<?xml version="1.0" encoding="us-ascii"?>
<!--XBRL document created with Toppan Merrill Bridge  10.1.0.3 -->
<!--Based on XBRL 2.1-->
<!--Created on: 11/1/2022 8:07:09 PM-->
<!--Modified on: 11/1/2022 8:07:09 PM-->
<link:linkbase xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" xmlns:bpmc="http://www.blueprintmedicines.com" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:xlink="http://www.w3.org/1999/xlink">
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss" roleURI="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#StatementCondensedConsolidatedStatementsOfStockholdersEquity" roleURI="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedStatementsOfStockholdersEquity" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureFinancingArrangementsTables" roleURI="http://www.blueprintmedicines.com/role/DisclosureFinancingArrangementsTables" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureProductRevenueReservesAndAllowancesTables" roleURI="http://www.blueprintmedicines.com/role/DisclosureProductRevenueReservesAndAllowancesTables" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureCollaborationAndLicenseAgreementsTables" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsTables" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureFinancingArrangementsGeneralInformationDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureFinancingArrangementsGeneralInformationDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureFinancingArrangementsRoyaltyAndSalesInformationDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureFinancingArrangementsRoyaltyAndSalesInformationDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureFinancingArrangementsLongTermDebtDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureFinancingArrangementsLongTermDebtDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureFinancingArrangementsRollForwardDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureFinancingArrangementsRollForwardDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureMarketableSecuritiesTabularDisclosureDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureMarketableSecuritiesTabularDisclosureDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureFairValueOfFinancialInstrumentsDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureFairValueOfFinancialInstrumentsDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureProductRevenueReservesAndAllowancesProductRevenueDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureProductRevenueReservesAndAllowancesProductRevenueDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureProductRevenueReservesAndAllowancesRevenueRelatedReservesDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureProductRevenueReservesAndAllowancesRevenueRelatedReservesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureCollaborationAndLicenseAgreementsGeneralInformationDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsGeneralInformationDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureCollaborationAndLicenseAgreementsTransactionPriceDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsTransactionPriceDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureCollaborationAndLicenseAgreementsEquityInvestmentDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsEquityInvestmentDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureCollaborationAndLicenseAgreementsSaleOfStockDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsSaleOfStockDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureCollaborationAndLicenseAgreementsManufacturingAndResearchAndDevelopmentServicesDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsManufacturingAndResearchAndDevelopmentServicesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureCollaborationAndLicenseAgreementsRevenueRecognizedDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsRevenueRecognizedDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureCollaborationAndLicenseAgreementsCollaborationLossSharingDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsCollaborationLossSharingDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureCollaborationAndLicenseAgreementsReductionInExpensesDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsReductionInExpensesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureCollaborationAndLicenseAgreementsChangeInContractWithCustomerLiabilityDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsChangeInContractWithCustomerLiabilityDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureCollaborationAndLicenseAgreementsContractAssetsAndLiabilitiesDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsContractAssetsAndLiabilitiesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureCollaborationAndLicenseAgreementsPerformanceObligationsDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsPerformanceObligationsDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureCollaborationAndLicenseAgreementsPerformanceObligationsDefaultDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsPerformanceObligationsDefaultDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureStockBasedCompensation2015StockOptionAndIncentivePlanDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensation2015StockOptionAndIncentivePlanDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureStockBasedCompensation2020InducementPlanDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensation2020InducementPlanDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureStockBasedCompensationUnrecognizedCompensationCostsDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensationUnrecognizedCompensationCostsDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureStockBasedCompensationRestrictedStockUnitsActivityDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensationRestrictedStockUnitsActivityDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureStockBasedCompensationEmployeeStockPurchasePlanDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensationEmployeeStockPurchasePlanDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureStockBasedCompensationStockBasedCompensationExpenseByTypeDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensationStockBasedCompensationExpenseByTypeDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureStockBasedCompensationStockBasedCompensationExpenseByClassificationDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensationStockBasedCompensationExpenseByClassificationDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureNetLossPerShareDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureNetLossPerShareDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureIncomeTaxesFinancingArrangementsDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureIncomeTaxesFinancingArrangementsDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureIncomeTaxesEquityInvestmentDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureIncomeTaxesEquityInvestmentDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureCommitmentsAndContingenciesPurchaseCommitmentsDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCommitmentsAndContingenciesPurchaseCommitmentsDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20220930.xsd#DisclosureCommitmentsAndContingenciesIndemnificationAgreementsDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCommitmentsAndContingenciesIndemnificationAgreementsDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <link:arcroleRef arcroleURI="http://www.esma.europa.eu/xbrl/esef/arcrole/wider-narrower" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/arcrole/esma-arcrole-2018-11-21.xsd#wider-narrower" />
  <link:roleRef roleURI="http://www.blueprintmedicines.com/role/DisclosureStandardAndCustomAxisDomainDefaults" xlink:href="bpmc-20220930.xsd#DisclosureStandardAndCustomAxisDomainDefaults" xlink:type="simple" />
  <roleRef xlink:type="simple" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-roles-2022.xsd#eedm" roleURI="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xmlns="http://www.xbrl.org/2003/linkbase" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default" />
  <definitionLink xlink:role="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xlink:type="extended" xlink:title="Extensible Enumeration Domain Members" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ForeignPlanMember" xlink:label="us-gaap_ForeignPlanMember" xlink:title="us-gaap_ForeignPlanMember" />
    <loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/country/2022/country-2022.xsd#country_CH" xlink:label="country_CH" xlink:title="country_CH" />
    <definitionArc xlink:type="arc" xlink:from="us-gaap_ForeignPlanMember" xlink:to="country_CH" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:title="definition:us-gaap_ForeignPlanMember To country_CH" order="1" priority="0" />
  </definitionLink>
  <link:definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureStandardAndCustomAxisDomainDefaults" xlink:type="extended" xlink:title="99900 - Disclosure - Standard And Custom Axis Domain Defaults">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_LegalEntityAxis" xlink:label="dei_LegalEntityAxis_1" xlink:title="dei_LegalEntityAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityDomain" xlink:label="dei_EntityDomain_1" xlink:title="dei_EntityDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="dei_LegalEntityAxis_1" xlink:to="dei_EntityDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:dei_LegalEntityAxis_1 To dei_EntityDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_StatementScenarioAxis" xlink:label="srt_StatementScenarioAxis_1" xlink:title="srt_StatementScenarioAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="srt_ScenarioUnspecifiedDomain_1" xlink:title="srt_ScenarioUnspecifiedDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_StatementScenarioAxis_1" xlink:to="srt_ScenarioUnspecifiedDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_StatementScenarioAxis_1 To srt_ScenarioUnspecifiedDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis_1" xlink:title="srt_ProductOrServiceAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain_1" xlink:title="srt_ProductsAndServicesDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_ProductOrServiceAxis_1" xlink:to="srt_ProductsAndServicesDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_ProductOrServiceAxis_1 To srt_ProductsAndServicesDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="us-gaap_StatementEquityComponentsAxis_1" xlink:title="us-gaap_StatementEquityComponentsAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EquityComponentDomain" xlink:label="us-gaap_EquityComponentDomain_1" xlink:title="us-gaap_EquityComponentDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_StatementEquityComponentsAxis_1" xlink:to="us-gaap_EquityComponentDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_StatementEquityComponentsAxis_1 To us-gaap_EquityComponentDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CumulativeEffectPeriodOfAdoptionAxis" xlink:label="srt_CumulativeEffectPeriodOfAdoptionAxis_1" xlink:title="srt_CumulativeEffectPeriodOfAdoptionAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CumulativeEffectPeriodOfAdoptionDomain" xlink:label="srt_CumulativeEffectPeriodOfAdoptionDomain_1" xlink:title="srt_CumulativeEffectPeriodOfAdoptionDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_CumulativeEffectPeriodOfAdoptionAxis_1" xlink:to="srt_CumulativeEffectPeriodOfAdoptionDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_CumulativeEffectPeriodOfAdoptionAxis_1 To srt_CumulativeEffectPeriodOfAdoptionDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SubsidiarySaleOfStockAxis" xlink:label="us-gaap_SubsidiarySaleOfStockAxis_1" xlink:title="us-gaap_SubsidiarySaleOfStockAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain_1" xlink:title="us-gaap_SaleOfStockNameOfTransactionDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_SubsidiarySaleOfStockAxis_1" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_SubsidiarySaleOfStockAxis_1 To us-gaap_SaleOfStockNameOfTransactionDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis_1" xlink:title="srt_CounterpartyNameAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain_1" xlink:title="srt_RepurchaseAgreementCounterpartyNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_CounterpartyNameAxis_1" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_CounterpartyNameAxis_1 To srt_RepurchaseAgreementCounterpartyNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentTypeAxis" xlink:label="us-gaap_InvestmentTypeAxis_1" xlink:title="us-gaap_InvestmentTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentTypeCategorizationMember" xlink:label="us-gaap_InvestmentTypeCategorizationMember_1" xlink:title="us-gaap_InvestmentTypeCategorizationMember_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_InvestmentTypeAxis_1" xlink:to="us-gaap_InvestmentTypeCategorizationMember_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_InvestmentTypeAxis_1 To us-gaap_InvestmentTypeCategorizationMember_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueByMeasurementFrequencyAxis" xlink:label="us-gaap_FairValueByMeasurementFrequencyAxis_1" xlink:title="us-gaap_FairValueByMeasurementFrequencyAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueMeasurementFrequencyDomain" xlink:label="us-gaap_FairValueMeasurementFrequencyDomain_1" xlink:title="us-gaap_FairValueMeasurementFrequencyDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_FairValueByMeasurementFrequencyAxis_1" xlink:to="us-gaap_FairValueMeasurementFrequencyDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_FairValueByMeasurementFrequencyAxis_1 To us-gaap_FairValueMeasurementFrequencyDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis_1" xlink:title="us-gaap_FairValueByFairValueHierarchyLevelAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1" xlink:title="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis_1" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_FairValueByFairValueHierarchyLevelAxis_1 To us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CashAndCashEquivalentsAxis" xlink:label="us-gaap_CashAndCashEquivalentsAxis_1" xlink:title="us-gaap_CashAndCashEquivalentsAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember" xlink:label="us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_1" xlink:title="us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_CashAndCashEquivalentsAxis_1" xlink:to="us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_CashAndCashEquivalentsAxis_1 To us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_BalanceSheetLocationAxis" xlink:label="us-gaap_BalanceSheetLocationAxis_1" xlink:title="us-gaap_BalanceSheetLocationAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="us-gaap_BalanceSheetLocationDomain_1" xlink:title="us-gaap_BalanceSheetLocationDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_BalanceSheetLocationAxis_1" xlink:to="us-gaap_BalanceSheetLocationDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_BalanceSheetLocationAxis_1 To us-gaap_BalanceSheetLocationDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:label="us-gaap_PropertyPlantAndEquipmentByTypeAxis_1" xlink:title="us-gaap_PropertyPlantAndEquipmentByTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:label="us-gaap_PropertyPlantAndEquipmentTypeDomain_1" xlink:title="us-gaap_PropertyPlantAndEquipmentTypeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_PropertyPlantAndEquipmentByTypeAxis_1" xlink:to="us-gaap_PropertyPlantAndEquipmentTypeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_PropertyPlantAndEquipmentByTypeAxis_1 To us-gaap_PropertyPlantAndEquipmentTypeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis_1" xlink:title="us-gaap_TypeOfArrangementAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember_1" xlink:title="us-gaap_ArrangementsAndNonarrangementTransactionsMember_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_TypeOfArrangementAxis_1" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_TypeOfArrangementAxis_1 To us-gaap_ArrangementsAndNonarrangementTransactionsMember_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="us-gaap_IncomeStatementLocationAxis_1" xlink:title="us-gaap_IncomeStatementLocationAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain_1" xlink:title="us-gaap_IncomeStatementLocationDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_IncomeStatementLocationAxis_1" xlink:to="us-gaap_IncomeStatementLocationDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_IncomeStatementLocationAxis_1 To us-gaap_IncomeStatementLocationDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PlanNameAxis" xlink:label="us-gaap_PlanNameAxis_1" xlink:title="us-gaap_PlanNameAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PlanNameDomain" xlink:label="us-gaap_PlanNameDomain_1" xlink:title="us-gaap_PlanNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_PlanNameAxis_1" xlink:to="us-gaap_PlanNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_PlanNameAxis_1 To us-gaap_PlanNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis_1" xlink:title="us-gaap_AwardTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1" xlink:title="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_AwardTypeAxis_1" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_AwardTypeAxis_1 To us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_1" xlink:title="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AntidilutiveSecuritiesNameDomain" xlink:label="us-gaap_AntidilutiveSecuritiesNameDomain_1" xlink:title="us-gaap_AntidilutiveSecuritiesNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_1" xlink:to="us-gaap_AntidilutiveSecuritiesNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_1 To us-gaap_AntidilutiveSecuritiesNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RangeAxis" xlink:label="srt_RangeAxis_1" xlink:title="srt_RangeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RangeMember" xlink:label="srt_RangeMember_1" xlink:title="srt_RangeMember_1" />
    <link:definitionArc xlink:type="arc" xlink:from="srt_RangeAxis_1" xlink:to="srt_RangeMember_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:srt_RangeAxis_1 To srt_RangeMember_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:label="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis_1" xlink:title="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TypeOfAdoptionMember" xlink:label="us-gaap_TypeOfAdoptionMember_1" xlink:title="us-gaap_TypeOfAdoptionMember_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis_1" xlink:to="us-gaap_TypeOfAdoptionMember_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_AdjustmentsForNewAccountingPronouncementsAxis_1 To us-gaap_TypeOfAdoptionMember_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncomeTaxAuthorityAxis" xlink:label="us-gaap_IncomeTaxAuthorityAxis_1" xlink:title="us-gaap_IncomeTaxAuthorityAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncomeTaxAuthorityDomain" xlink:label="us-gaap_IncomeTaxAuthorityDomain_1" xlink:title="us-gaap_IncomeTaxAuthorityDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_IncomeTaxAuthorityAxis_1" xlink:to="us-gaap_IncomeTaxAuthorityDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_IncomeTaxAuthorityAxis_1 To us-gaap_IncomeTaxAuthorityDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TaxCreditCarryforwardAxis" xlink:label="us-gaap_TaxCreditCarryforwardAxis_1" xlink:title="us-gaap_TaxCreditCarryforwardAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TaxCreditCarryforwardNameDomain" xlink:label="us-gaap_TaxCreditCarryforwardNameDomain_1" xlink:title="us-gaap_TaxCreditCarryforwardNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_TaxCreditCarryforwardAxis_1" xlink:to="us-gaap_TaxCreditCarryforwardNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_TaxCreditCarryforwardAxis_1 To us-gaap_TaxCreditCarryforwardNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SubsequentEventTypeAxis" xlink:label="us-gaap_SubsequentEventTypeAxis_1" xlink:title="us-gaap_SubsequentEventTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="us-gaap_SubsequentEventTypeDomain_1" xlink:title="us-gaap_SubsequentEventTypeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_SubsequentEventTypeAxis_1" xlink:to="us-gaap_SubsequentEventTypeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_SubsequentEventTypeAxis_1 To us-gaap_SubsequentEventTypeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AssetAcquisitionAxis" xlink:label="us-gaap_AssetAcquisitionAxis_1" xlink:title="us-gaap_AssetAcquisitionAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AssetAcquisitionDomain" xlink:label="us-gaap_AssetAcquisitionDomain_1" xlink:title="us-gaap_AssetAcquisitionDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_AssetAcquisitionAxis_1" xlink:to="us-gaap_AssetAcquisitionDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_AssetAcquisitionAxis_1 To us-gaap_AssetAcquisitionDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LossContingenciesByNatureOfContingencyAxis" xlink:label="us-gaap_LossContingenciesByNatureOfContingencyAxis_1" xlink:title="us-gaap_LossContingenciesByNatureOfContingencyAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LossContingencyNatureDomain" xlink:label="us-gaap_LossContingencyNatureDomain_1" xlink:title="us-gaap_LossContingencyNatureDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_LossContingenciesByNatureOfContingencyAxis_1" xlink:to="us-gaap_LossContingencyNatureDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_LossContingenciesByNatureOfContingencyAxis_1 To us-gaap_LossContingencyNatureDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongtermDebtTypeAxis" xlink:label="us-gaap_LongtermDebtTypeAxis_1" xlink:title="us-gaap_LongtermDebtTypeAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongtermDebtTypeDomain" xlink:label="us-gaap_LongtermDebtTypeDomain_1" xlink:title="us-gaap_LongtermDebtTypeDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_LongtermDebtTypeAxis_1" xlink:to="us-gaap_LongtermDebtTypeDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_LongtermDebtTypeAxis_1 To us-gaap_LongtermDebtTypeDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis_1" xlink:title="us-gaap_DebtInstrumentAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain_1" xlink:title="us-gaap_DebtInstrumentNameDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_DebtInstrumentAxis_1" xlink:to="us-gaap_DebtInstrumentNameDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_DebtInstrumentAxis_1 To us-gaap_DebtInstrumentNameDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_VariableRateAxis" xlink:label="us-gaap_VariableRateAxis_1" xlink:title="us-gaap_VariableRateAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_VariableRateDomain" xlink:label="us-gaap_VariableRateDomain_1" xlink:title="us-gaap_VariableRateDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_VariableRateAxis_1" xlink:to="us-gaap_VariableRateDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_VariableRateAxis_1 To us-gaap_VariableRateDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="us-gaap_FinancialInstrumentAxis_1" xlink:title="us-gaap_FinancialInstrumentAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1" xlink:title="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_FinancialInstrumentAxis_1" xlink:to="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_FinancialInstrumentAxis_1 To us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1" order="1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:label="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1" xlink:title="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RelatedPartyDomain" xlink:label="us-gaap_RelatedPartyDomain_1" xlink:title="us-gaap_RelatedPartyDomain_1" />
    <link:definitionArc xlink:type="arc" xlink:from="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1" xlink:to="us-gaap_RelatedPartyDomain_1" use="optional" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:title="definition:us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_1 To us-gaap_RelatedPartyDomain_1" order="1" />
  </link:definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss" xlink:type="extended" xlink:title="00200 - Statement - Condensed Consolidated Statements of Operations and Comprehensive Loss" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="srt_ProductOrServiceAxis" priority="2" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProductMember" xlink:label="us-gaap_ProductMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ProductsAndServicesDomain" xlink:to="us-gaap_ProductMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborationAndLicenseMember" xlink:label="bpmc_CollaborationAndLicenseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_ProductsAndServicesDomain" xlink:to="bpmc_CollaborationAndLicenseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborationAndLicenseExcludingRelatedPartyMember" xlink:label="bpmc_CollaborationAndLicenseExcludingRelatedPartyMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_CollaborationAndLicenseMember" xlink:to="bpmc_CollaborationAndLicenseExcludingRelatedPartyMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborationAndLicenseRelatedPartyMember" xlink:label="bpmc_CollaborationAndLicenseRelatedPartyMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="bpmc_CollaborationAndLicenseMember" xlink:to="bpmc_CollaborationAndLicenseRelatedPartyMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LicenseMember" xlink:label="us-gaap_LicenseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_CollaborationAndLicenseRelatedPartyMember" xlink:to="us-gaap_LicenseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_LicenseRelatedPartyMember" xlink:label="bpmc_LicenseRelatedPartyMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_LicenseMember" xlink:to="bpmc_LicenseRelatedPartyMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenuesAbstract" xlink:label="us-gaap_RevenuesAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_RevenuesAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_RevenuesAbstract" xlink:to="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingExpensesAbstract" xlink:label="us-gaap_OperatingExpensesAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OperatingExpensesAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="us-gaap_CostOfGoodsAndServicesSold" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_OperatingExpensesAbstract" xlink:to="us-gaap_CostOfGoodsAndServicesSold" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ResearchAndDevelopmentExpense" xlink:label="us-gaap_ResearchAndDevelopmentExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_OperatingExpensesAbstract" xlink:to="us-gaap_ResearchAndDevelopmentExpense" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SellingGeneralAndAdministrativeExpense" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_OperatingExpensesAbstract" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpense" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborationProfitLossSharing" xlink:label="bpmc_CollaborationProfitLossSharing" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_OperatingExpensesAbstract" xlink:to="bpmc_CollaborationProfitLossSharing" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostsAndExpenses" xlink:label="us-gaap_CostsAndExpenses" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_OperatingExpensesAbstract" xlink:to="us-gaap_CostsAndExpenses" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NonoperatingIncomeExpenseAbstract" xlink:label="us-gaap_NonoperatingIncomeExpenseAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NonoperatingIncomeExpenseAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InterestIncomeExpenseNet" xlink:label="us-gaap_InterestIncomeExpenseNet" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_NonoperatingIncomeExpenseAbstract" xlink:to="us-gaap_InterestIncomeExpenseNet" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="us-gaap_OtherNonoperatingIncomeExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_NonoperatingIncomeExpenseAbstract" xlink:to="us-gaap_OtherNonoperatingIncomeExpense" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NonoperatingIncomeExpense" xlink:label="us-gaap_NonoperatingIncomeExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_NonoperatingIncomeExpenseAbstract" xlink:to="us-gaap_NonoperatingIncomeExpense" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:label="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncomeTaxExpenseBenefit" xlink:label="us-gaap_IncomeTaxExpenseBenefit" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_IncomeTaxExpenseBenefit" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NetIncomeLoss" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract" xlink:label="us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:label="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract" xlink:to="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" xlink:label="us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract" xlink:to="us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_ComprehensiveIncomeNetOfTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EarningsPerShareBasic" xlink:label="us-gaap_EarningsPerShareBasic" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_EarningsPerShareBasic" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EarningsPerShareDiluted" xlink:label="us-gaap_EarningsPerShareDiluted" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_EarningsPerShareDiluted" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="12" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:label="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="13" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedStatementsOfStockholdersEquity" xlink:type="extended" xlink:title="00300 - Statement - Condensed Consolidated Statements of Stockholders' Equity" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="us-gaap_StatementEquityComponentsAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_StatementEquityComponentsAxis" priority="2" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EquityComponentDomain" xlink:label="us-gaap_EquityComponentDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_StatementEquityComponentsAxis" xlink:to="us-gaap_EquityComponentDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ParentMember" xlink:label="us-gaap_ParentMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_ParentMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CommonStockMember" xlink:label="us-gaap_CommonStockMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ParentMember" xlink:to="us-gaap_CommonStockMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AdditionalPaidInCapitalMember" xlink:label="us-gaap_AdditionalPaidInCapitalMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ParentMember" xlink:to="us-gaap_AdditionalPaidInCapitalMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ParentMember" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RetainedEarningsMember" xlink:label="us-gaap_RetainedEarningsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ParentMember" xlink:to="us-gaap_RetainedEarningsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:label="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockholdersEquity" xlink:label="us-gaap_StockholdersEquity" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_StockholdersEquity" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CommonStockSharesIssued" xlink:label="us-gaap_CommonStockSharesIssued" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_CommonStockSharesIssued" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation" xlink:label="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:label="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation" xlink:to="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan" xlink:label="us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" xlink:label="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan" xlink:to="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:label="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodValueNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_StockIssuedDuringPeriodValueNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent" xlink:label="us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_NetIncomeLoss" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureFinancingArrangementsTables" xlink:type="extended" xlink:title="30303 - Disclosure - Financing Arrangements (Tables)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentTable" xlink:label="us-gaap_DebtInstrumentTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_DebtInstrumentTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RoyaltyPharmaRoyaltyPurchaseAgreementMember" xlink:label="bpmc_RoyaltyPharmaRoyaltyPurchaseAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="bpmc_RoyaltyPharmaRoyaltyPurchaseAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFutureRevenuePurchaseAgreementMember" xlink:label="bpmc_SixthStreetPartnersFutureRevenuePurchaseAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="bpmc_SixthStreetPartnersFutureRevenuePurchaseAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFinancingAgreementMember" xlink:label="bpmc_SixthStreetPartnersFinancingAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="bpmc_SixthStreetPartnersFinancingAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilitiesMember" xlink:label="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilitiesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_SixthStreetPartnersFinancingAgreementMember" xlink:to="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilitiesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilityMember" xlink:label="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilityMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilitiesMember" xlink:to="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilityMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentLineItems" xlink:label="us-gaap_DebtInstrumentLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_DebtInstrumentTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TableTextBlock" xlink:label="us-gaap_TableTextBlock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_TableTextBlock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfDebtInstrumentsTextBlock" xlink:label="us-gaap_ScheduleOfDebtInstrumentsTextBlock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_TableTextBlock" xlink:to="us-gaap_ScheduleOfDebtInstrumentsTextBlock" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureProductRevenueReservesAndAllowancesTables" xlink:type="extended" xlink:title="30603 - Disclosure - Product Revenue Reserves and Allowances (Tables)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DisaggregationOfRevenueTable" xlink:label="us-gaap_DisaggregationOfRevenueTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_DisaggregationOfRevenueTable" xlink:to="srt_ProductOrServiceAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProductMember" xlink:label="us-gaap_ProductMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ProductsAndServicesDomain" xlink:to="us-gaap_ProductMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="us-gaap_DisaggregationOfRevenueLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_DisaggregationOfRevenueLineItems" xlink:to="us-gaap_DisaggregationOfRevenueTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TableTextBlock" xlink:label="us-gaap_TableTextBlock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DisaggregationOfRevenueLineItems" xlink:to="us-gaap_TableTextBlock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DisaggregationOfRevenueTableTextBlock" xlink:label="us-gaap_DisaggregationOfRevenueTableTextBlock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_TableTextBlock" xlink:to="us-gaap_DisaggregationOfRevenueTableTextBlock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerAssetAndLiabilityTableTextBlock" xlink:label="us-gaap_ContractWithCustomerAssetAndLiabilityTableTextBlock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_TableTextBlock" xlink:to="us-gaap_ContractWithCustomerAssetAndLiabilityTableTextBlock" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsTables" xlink:type="extended" xlink:title="31003 - Disclosure - Collaboration and License Agreements (Tables)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" priority="2" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheMember" xlink:label="bpmc_RocheMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_RocheMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationPralsetnibAgreementMember" xlink:label="bpmc_RocheCollaborationPralsetnibAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationPralsetnibAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" xlink:label="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CStoneMember" xlink:label="bpmc_CStoneMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_CStoneMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_ProductOrServiceAxis" priority="2" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborationAndLicenseMember" xlink:label="bpmc_CollaborationAndLicenseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ProductsAndServicesDomain" xlink:to="bpmc_CollaborationAndLicenseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborationMember" xlink:label="bpmc_CollaborationMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_CollaborationAndLicenseMember" xlink:to="bpmc_CollaborationMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TableTextBlock" xlink:label="us-gaap_TableTextBlock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_TableTextBlock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ScheduleOfManufacturingServicesRelatedToAgreementActivitiesTableTextBlock" xlink:label="bpmc_ScheduleOfManufacturingServicesRelatedToAgreementActivitiesTableTextBlock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_TableTextBlock" xlink:to="bpmc_ScheduleOfManufacturingServicesRelatedToAgreementActivitiesTableTextBlock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DisaggregationOfRevenueTableTextBlock" xlink:label="us-gaap_DisaggregationOfRevenueTableTextBlock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_TableTextBlock" xlink:to="us-gaap_DisaggregationOfRevenueTableTextBlock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ScheduleOfCollaborationLossSharingTableTextBlock" xlink:label="bpmc_ScheduleOfCollaborationLossSharingTableTextBlock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_TableTextBlock" xlink:to="bpmc_ScheduleOfCollaborationLossSharingTableTextBlock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ScheduleOfAmountsRecognizedAsReductionsToExpensesCollaborativeArrangementTableTextBlock" xlink:label="bpmc_ScheduleOfAmountsRecognizedAsReductionsToExpensesCollaborativeArrangementTableTextBlock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_TableTextBlock" xlink:to="bpmc_ScheduleOfAmountsRecognizedAsReductionsToExpensesCollaborativeArrangementTableTextBlock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerAssetAndLiabilityTableTextBlock" xlink:label="us-gaap_ContractWithCustomerAssetAndLiabilityTableTextBlock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_TableTextBlock" xlink:to="us-gaap_ContractWithCustomerAssetAndLiabilityTableTextBlock" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureFinancingArrangementsGeneralInformationDetails" xlink:type="extended" xlink:title="40301 - Disclosure - Financing Arrangements - General Information (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentTable" xlink:label="us-gaap_DebtInstrumentTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongtermDebtTypeAxis" xlink:label="us-gaap_LongtermDebtTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_DebtInstrumentTable" xlink:to="us-gaap_LongtermDebtTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongtermDebtTypeDomain" xlink:label="us-gaap_LongtermDebtTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_LongtermDebtTypeAxis" xlink:to="us-gaap_LongtermDebtTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SaleOfFutureRoyaltiesAndRevenuesMember" xlink:label="bpmc_SaleOfFutureRoyaltiesAndRevenuesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_LongtermDebtTypeDomain" xlink:to="bpmc_SaleOfFutureRoyaltiesAndRevenuesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LoansPayableMember" xlink:label="us-gaap_LoansPayableMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_LongtermDebtTypeDomain" xlink:to="us-gaap_LoansPayableMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SecuredDebtMember" xlink:label="us-gaap_SecuredDebtMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_LongtermDebtTypeDomain" xlink:to="us-gaap_SecuredDebtMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_DebtInstrumentTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RoyaltyPharmaRoyaltyPurchaseAgreementMember" xlink:label="bpmc_RoyaltyPharmaRoyaltyPurchaseAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="bpmc_RoyaltyPharmaRoyaltyPurchaseAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFinancingArrangementsMember" xlink:label="bpmc_SixthStreetPartnersFinancingArrangementsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="bpmc_SixthStreetPartnersFinancingArrangementsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFutureRevenuePurchaseAgreementMember" xlink:label="bpmc_SixthStreetPartnersFutureRevenuePurchaseAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_SixthStreetPartnersFinancingArrangementsMember" xlink:to="bpmc_SixthStreetPartnersFutureRevenuePurchaseAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFinancingAgreementMember" xlink:label="bpmc_SixthStreetPartnersFinancingAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="bpmc_SixthStreetPartnersFinancingArrangementsMember" xlink:to="bpmc_SixthStreetPartnersFinancingAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilitiesMember" xlink:label="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilitiesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_SixthStreetPartnersFinancingAgreementMember" xlink:to="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilitiesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilityMember" xlink:label="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilityMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilitiesMember" xlink:to="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilityMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredDelayedDrawTermLoanFacilityMember" xlink:label="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredDelayedDrawTermLoanFacilityMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilitiesMember" xlink:to="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredDelayedDrawTermLoanFacilityMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_VariableRateAxis" xlink:label="us-gaap_VariableRateAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_DebtInstrumentTable" xlink:to="us-gaap_VariableRateAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_VariableRateDomain" xlink:label="us-gaap_VariableRateDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_VariableRateAxis" xlink:to="us-gaap_VariableRateDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SecuredOvernightFinancingRateSofrOvernightIndexSwapRateMember" xlink:label="us-gaap_SecuredOvernightFinancingRateSofrOvernightIndexSwapRateMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_VariableRateDomain" xlink:to="us-gaap_SecuredOvernightFinancingRateSofrOvernightIndexSwapRateMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_BaseRateMember" xlink:label="us-gaap_BaseRateMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_VariableRateDomain" xlink:to="us-gaap_BaseRateMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentLineItems" xlink:label="us-gaap_DebtInstrumentLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_DebtInstrumentTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentsAbstract" xlink:label="us-gaap_DebtInstrumentsAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_DebtInstrumentsAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentIssuanceDate1" xlink:label="us-gaap_DebtInstrumentIssuanceDate1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentsAbstract" xlink:to="us-gaap_DebtInstrumentIssuanceDate1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_DebtInstrumentTransactionsNumber" xlink:label="bpmc_DebtInstrumentTransactionsNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentsAbstract" xlink:to="bpmc_DebtInstrumentTransactionsNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentFaceAmount" xlink:label="us-gaap_DebtInstrumentFaceAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_DebtInstrumentsAbstract" xlink:to="us-gaap_DebtInstrumentFaceAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_DebtInstrumentFaceAmountPotentialAmount" xlink:label="bpmc_DebtInstrumentFaceAmountPotentialAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_DebtInstrumentsAbstract" xlink:to="bpmc_DebtInstrumentFaceAmountPotentialAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_DebtInstrumentTranchesNumber" xlink:label="bpmc_DebtInstrumentTranchesNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_DebtInstrumentsAbstract" xlink:to="bpmc_DebtInstrumentTranchesNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentMaturityDate" xlink:label="us-gaap_DebtInstrumentMaturityDate" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_DebtInstrumentsAbstract" xlink:to="us-gaap_DebtInstrumentMaturityDate" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentBasisSpreadOnVariableRate1" xlink:label="us-gaap_DebtInstrumentBasisSpreadOnVariableRate1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_DebtInstrumentsAbstract" xlink:to="us-gaap_DebtInstrumentBasisSpreadOnVariableRate1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_DebtInstrumentVariableRateFloor" xlink:label="bpmc_DebtInstrumentVariableRateFloor" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_DebtInstrumentsAbstract" xlink:to="bpmc_DebtInstrumentVariableRateFloor" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DeferredFinanceCostsGross" xlink:label="us-gaap_DeferredFinanceCostsGross" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_DebtInstrumentsAbstract" xlink:to="us-gaap_DeferredFinanceCostsGross" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet" xlink:label="us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_DebtInstrumentsAbstract" xlink:to="us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_DebtInstrumentCovenantsConsolidatedLiquidityPeriodCommencingFromDateTermLoanFundedToDateDayBeforeNextTermLoansFunded" xlink:label="bpmc_DebtInstrumentCovenantsConsolidatedLiquidityPeriodCommencingFromDateTermLoanFundedToDateDayBeforeNextTermLoansFunded" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_DebtInstrumentsAbstract" xlink:to="bpmc_DebtInstrumentCovenantsConsolidatedLiquidityPeriodCommencingFromDateTermLoanFundedToDateDayBeforeNextTermLoansFunded" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_DebtInstrumentCovenantsConsolidatedLiquidityPeriodCommencingFromDateTermLoanFundedToDateDayBeforeNextTermLoansFundedEachDayThereafter" xlink:label="bpmc_DebtInstrumentCovenantsConsolidatedLiquidityPeriodCommencingFromDateTermLoanFundedToDateDayBeforeNextTermLoansFundedEachDayThereafter" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="12" xlink:from="us-gaap_DebtInstrumentsAbstract" xlink:to="bpmc_DebtInstrumentCovenantsConsolidatedLiquidityPeriodCommencingFromDateTermLoanFundedToDateDayBeforeNextTermLoansFundedEachDayThereafter" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromIssuanceOfLongTermDebtAbstract" xlink:label="us-gaap_ProceedsFromIssuanceOfLongTermDebtAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_ProceedsFromIssuanceOfLongTermDebtAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromIssuanceOfLongTermDebt" xlink:label="us-gaap_ProceedsFromIssuanceOfLongTermDebt" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ProceedsFromIssuanceOfLongTermDebtAbstract" xlink:to="us-gaap_ProceedsFromIssuanceOfLongTermDebt" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentageAbstract" xlink:label="us-gaap_DebtInstrumentInterestRateEffectivePercentageAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_DebtInstrumentInterestRateEffectivePercentageAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage" xlink:label="us-gaap_DebtInstrumentInterestRateEffectivePercentage" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentInterestRateEffectivePercentageAbstract" xlink:to="us-gaap_DebtInstrumentInterestRateEffectivePercentage" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureFinancingArrangementsRoyaltyAndSalesInformationDetails" xlink:type="extended" xlink:title="40302 - Disclosure - Financing Arrangements - Royalty and Sales Information (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentTable" xlink:label="us-gaap_DebtInstrumentTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_DebtInstrumentTable" xlink:to="srt_CounterpartyNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersMember" xlink:label="bpmc_SixthStreetPartnersMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_SixthStreetPartnersMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentLineItems" xlink:label="us-gaap_DebtInstrumentLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_DebtInstrumentTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesPercentageRate" xlink:label="bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesPercentageRate" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesPercentageRate" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesAmountMaximum" xlink:label="bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesAmountMaximum" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesAmountMaximum" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesCumulativeCapOfUpfrontInvestedCapitalRatio" xlink:label="bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesCumulativeCapOfUpfrontInvestedCapitalRatio" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesCumulativeCapOfUpfrontInvestedCapitalRatio" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesCumulativeCapOfUpfrontInvestedCapitalAmount" xlink:label="bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesCumulativeCapOfUpfrontInvestedCapitalAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesCumulativeCapOfUpfrontInvestedCapitalAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesCumulativeCapOfUpfrontInvestedCapitalRevenueTargetsNotAchievedPercentageIncrease" xlink:label="bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesCumulativeCapOfUpfrontInvestedCapitalRevenueTargetsNotAchievedPercentageIncrease" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesCumulativeCapOfUpfrontInvestedCapitalRevenueTargetsNotAchievedPercentageIncrease" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesCumulativeCapOfUpfrontInvestedCapitalRevenueTargetsNotAchievedRatio" xlink:label="bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesCumulativeCapOfUpfrontInvestedCapitalRevenueTargetsNotAchievedRatio" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesCumulativeCapOfUpfrontInvestedCapitalRevenueTargetsNotAchievedRatio" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesCumulativeCapOfUpfrontInvestedCapitalRevenueTargetsNotAchievedAmount" xlink:label="bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesCumulativeCapOfUpfrontInvestedCapitalRevenueTargetsNotAchievedAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="bpmc_PurchaseAndSaleAgreementRoyaltiesFutureRoyaltyPaymentsAnnualWorldwideNetProductSalesCumulativeCapOfUpfrontInvestedCapitalRevenueTargetsNotAchievedAmount" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureFinancingArrangementsLongTermDebtDetails" xlink:type="extended" xlink:title="40303 - Disclosure - Financing Arrangements - Long-term Debt (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentTable" xlink:label="us-gaap_DebtInstrumentTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongtermDebtTypeAxis" xlink:label="us-gaap_LongtermDebtTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_DebtInstrumentTable" xlink:to="us-gaap_LongtermDebtTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongtermDebtTypeDomain" xlink:label="us-gaap_LongtermDebtTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_LongtermDebtTypeAxis" xlink:to="us-gaap_LongtermDebtTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SaleOfFutureRoyaltiesAndRevenuesMember" xlink:label="bpmc_SaleOfFutureRoyaltiesAndRevenuesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_LongtermDebtTypeDomain" xlink:to="bpmc_SaleOfFutureRoyaltiesAndRevenuesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_DebtInstrumentTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RoyaltyPharmaRoyaltyPurchaseAgreementMember" xlink:label="bpmc_RoyaltyPharmaRoyaltyPurchaseAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="bpmc_RoyaltyPharmaRoyaltyPurchaseAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFinancingArrangementsMember" xlink:label="bpmc_SixthStreetPartnersFinancingArrangementsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="bpmc_SixthStreetPartnersFinancingArrangementsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFutureRevenuePurchaseAgreementMember" xlink:label="bpmc_SixthStreetPartnersFutureRevenuePurchaseAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_SixthStreetPartnersFinancingArrangementsMember" xlink:to="bpmc_SixthStreetPartnersFutureRevenuePurchaseAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentLineItems" xlink:label="us-gaap_DebtInstrumentLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_DebtInstrumentTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtAndCapitalLeaseObligationsIncludingCurrentMaturitiesAbstract" xlink:label="us-gaap_LongTermDebtAndCapitalLeaseObligationsIncludingCurrentMaturitiesAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_LongTermDebtAndCapitalLeaseObligationsIncludingCurrentMaturitiesAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtAbstract" xlink:label="us-gaap_LongTermDebtAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_LongTermDebtAndCapitalLeaseObligationsIncludingCurrentMaturitiesAbstract" xlink:to="us-gaap_LongTermDebtAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebt" xlink:label="us-gaap_LongTermDebt" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_LongTermDebtAbstract" xlink:to="us-gaap_LongTermDebt" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureFinancingArrangementsRollForwardDetails" xlink:type="extended" xlink:title="40304 - Disclosure - Financing Arrangements - Roll Forward (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentTable" xlink:label="us-gaap_DebtInstrumentTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongtermDebtTypeAxis" xlink:label="us-gaap_LongtermDebtTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_DebtInstrumentTable" xlink:to="us-gaap_LongtermDebtTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongtermDebtTypeDomain" xlink:label="us-gaap_LongtermDebtTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_LongtermDebtTypeAxis" xlink:to="us-gaap_LongtermDebtTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SaleOfFutureRoyaltiesAndRevenuesMember" xlink:label="bpmc_SaleOfFutureRoyaltiesAndRevenuesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_LongtermDebtTypeDomain" xlink:to="bpmc_SaleOfFutureRoyaltiesAndRevenuesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SecuredDebtMember" xlink:label="us-gaap_SecuredDebtMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_LongtermDebtTypeDomain" xlink:to="us-gaap_SecuredDebtMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_DebtInstrumentTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RoyaltyPharmaRoyaltyPurchaseAgreementMember" xlink:label="bpmc_RoyaltyPharmaRoyaltyPurchaseAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="bpmc_RoyaltyPharmaRoyaltyPurchaseAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFinancingArrangementsMember" xlink:label="bpmc_SixthStreetPartnersFinancingArrangementsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="bpmc_SixthStreetPartnersFinancingArrangementsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFutureRevenuePurchaseAgreementMember" xlink:label="bpmc_SixthStreetPartnersFutureRevenuePurchaseAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_SixthStreetPartnersFinancingArrangementsMember" xlink:to="bpmc_SixthStreetPartnersFutureRevenuePurchaseAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFinancingAgreementMember" xlink:label="bpmc_SixthStreetPartnersFinancingAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="bpmc_SixthStreetPartnersFinancingArrangementsMember" xlink:to="bpmc_SixthStreetPartnersFinancingAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilitiesMember" xlink:label="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilitiesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_SixthStreetPartnersFinancingAgreementMember" xlink:to="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilitiesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilityMember" xlink:label="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilityMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilitiesMember" xlink:to="bpmc_SixthStreetPartnersFinancingAgreementSeniorSecuredTermLoanFacilityMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentLineItems" xlink:label="us-gaap_DebtInstrumentLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_DebtInstrumentTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtAndCapitalLeaseObligationsIncludingCurrentMaturitiesAbstract" xlink:label="us-gaap_LongTermDebtAndCapitalLeaseObligationsIncludingCurrentMaturitiesAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_LongTermDebtAndCapitalLeaseObligationsIncludingCurrentMaturitiesAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtAbstract" xlink:label="us-gaap_LongTermDebtAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_LongTermDebtAndCapitalLeaseObligationsIncludingCurrentMaturitiesAbstract" xlink:to="us-gaap_LongTermDebtAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebt" xlink:label="us-gaap_LongTermDebt" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_LongTermDebtAbstract" xlink:to="us-gaap_LongTermDebt" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromIssuanceOfLongTermDebt" xlink:label="us-gaap_ProceedsFromIssuanceOfLongTermDebt" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_LongTermDebtAbstract" xlink:to="us-gaap_ProceedsFromIssuanceOfLongTermDebt" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InterestExpenseDebtExcludingAmortization" xlink:label="us-gaap_InterestExpenseDebtExcludingAmortization" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_LongTermDebtAbstract" xlink:to="us-gaap_InterestExpenseDebtExcludingAmortization" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_DebtDiscountsAndCapitalizedDebtClosingCosts" xlink:label="bpmc_DebtDiscountsAndCapitalizedDebtClosingCosts" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_LongTermDebtAbstract" xlink:to="bpmc_DebtDiscountsAndCapitalizedDebtClosingCosts" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InterestPaid" xlink:label="us-gaap_InterestPaid" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_LongTermDebtAbstract" xlink:to="us-gaap_InterestPaid" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureMarketableSecuritiesTabularDisclosureDetails" xlink:type="extended" xlink:title="40401 - Disclosure - Marketable Securities - Tabular Disclosure (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="us-gaap_FinancialInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_DebtSecuritiesAvailableForSaleTable" xlink:to="us-gaap_FinancialInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FinancialInstrumentAxis" xlink:to="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_USGovernmentCorporationsAndAgenciesSecuritiesMember" xlink:label="us-gaap_USGovernmentCorporationsAndAgenciesSecuritiesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="us-gaap_USGovernmentCorporationsAndAgenciesSecuritiesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_USTreasurySecuritiesMember" xlink:label="us-gaap_USTreasurySecuritiesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="us-gaap_USTreasurySecuritiesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:label="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:label="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:to="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostAfterAllowanceForCreditLoss" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostAfterAllowanceForCreditLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostAfterAllowanceForCreditLoss" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureFairValueOfFinancialInstrumentsDetails" xlink:type="extended" xlink:title="40501 - Disclosure - Fair Value of Financial Instruments (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueByMeasurementFrequencyAxis" xlink:label="us-gaap_FairValueByMeasurementFrequencyAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueByMeasurementFrequencyAxis" priority="2" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueMeasurementFrequencyDomain" xlink:label="us-gaap_FairValueMeasurementFrequencyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByMeasurementFrequencyAxis" xlink:to="us-gaap_FairValueMeasurementFrequencyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueMeasurementsRecurringMember" xlink:label="us-gaap_FairValueMeasurementsRecurringMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FairValueMeasurementFrequencyDomain" xlink:to="us-gaap_FairValueMeasurementsRecurringMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueByFairValueHierarchyLevelAxis" priority="2" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueInputsLevel12And3Member" xlink:label="us-gaap_FairValueInputsLevel12And3Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueInputsLevel12And3Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueInputsLevel1Member" xlink:label="us-gaap_FairValueInputsLevel1Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FairValueInputsLevel12And3Member" xlink:to="us-gaap_FairValueInputsLevel1Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueInputsLevel2Member" xlink:label="us-gaap_FairValueInputsLevel2Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FairValueInputsLevel12And3Member" xlink:to="us-gaap_FairValueInputsLevel2Member" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CashAndCashEquivalentsAxis" xlink:label="us-gaap_CashAndCashEquivalentsAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_CashAndCashEquivalentsAxis" priority="2" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember" xlink:label="us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_CashAndCashEquivalentsAxis" xlink:to="us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CashEquivalentsMember" xlink:label="us-gaap_CashEquivalentsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember" xlink:to="us-gaap_CashEquivalentsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_MoneyMarketFundsMember" xlink:label="us-gaap_MoneyMarketFundsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_CashEquivalentsMember" xlink:to="us-gaap_MoneyMarketFundsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="us-gaap_FinancialInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="4" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FinancialInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FinancialInstrumentAxis" xlink:to="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_USGovernmentCorporationsAndAgenciesSecuritiesMember" xlink:label="us-gaap_USGovernmentCorporationsAndAgenciesSecuritiesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="us-gaap_USGovernmentCorporationsAndAgenciesSecuritiesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_USTreasurySecuritiesMember" xlink:label="us-gaap_USTreasurySecuritiesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="us-gaap_USTreasurySecuritiesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FairValueNetAssetLiabilityAbstract" xlink:label="us-gaap_FairValueNetAssetLiabilityAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueNetAssetLiabilityAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure" xlink:label="us-gaap_CashAndCashEquivalentsFairValueDisclosure" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FairValueNetAssetLiabilityAbstract" xlink:to="us-gaap_CashAndCashEquivalentsFairValueDisclosure" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FairValueNetAssetLiabilityAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AssetsFairValueDisclosure" xlink:label="us-gaap_AssetsFairValueDisclosure" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_FairValueNetAssetLiabilityAbstract" xlink:to="us-gaap_AssetsFairValueDisclosure" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureProductRevenueReservesAndAllowancesProductRevenueDetails" xlink:type="extended" xlink:title="40601 - Disclosure - Product Revenue Reserves and Allowances - Product Revenue (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DisaggregationOfRevenueTable" xlink:label="us-gaap_DisaggregationOfRevenueTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_DisaggregationOfRevenueTable" xlink:to="srt_ProductOrServiceAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProductMember" xlink:label="us-gaap_ProductMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ProductsAndServicesDomain" xlink:to="us-gaap_ProductMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_AyvakitAndAyvakytMember" xlink:label="bpmc_AyvakitAndAyvakytMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ProductMember" xlink:to="bpmc_AyvakitAndAyvakytMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_GavretoMember" xlink:label="bpmc_GavretoMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ProductMember" xlink:to="bpmc_GavretoMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="us-gaap_DisaggregationOfRevenueLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_DisaggregationOfRevenueLineItems" xlink:to="us-gaap_DisaggregationOfRevenueTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenuesAbstract" xlink:label="us-gaap_RevenuesAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DisaggregationOfRevenueLineItems" xlink:to="us-gaap_RevenuesAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_RevenuesAbstract" xlink:to="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureProductRevenueReservesAndAllowancesRevenueRelatedReservesDetails" xlink:type="extended" xlink:title="40603 - Disclosure - Product Revenue Reserves and Allowances - Revenue-related Reserves (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DisaggregationOfRevenueTable" xlink:label="us-gaap_DisaggregationOfRevenueTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_BalanceSheetLocationAxis" xlink:label="us-gaap_BalanceSheetLocationAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_DisaggregationOfRevenueTable" xlink:to="us-gaap_BalanceSheetLocationAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="us-gaap_BalanceSheetLocationDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_BalanceSheetLocationAxis" xlink:to="us-gaap_BalanceSheetLocationDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccountsReceivableMember" xlink:label="us-gaap_AccountsReceivableMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_BalanceSheetLocationDomain" xlink:to="us-gaap_AccountsReceivableMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccruedLiabilitiesMember" xlink:label="us-gaap_AccruedLiabilitiesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_BalanceSheetLocationDomain" xlink:to="us-gaap_AccruedLiabilitiesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="us-gaap_DisaggregationOfRevenueLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_DisaggregationOfRevenueLineItems" xlink:to="us-gaap_DisaggregationOfRevenueTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerAssetNetAbstract" xlink:label="us-gaap_ContractWithCustomerAssetNetAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DisaggregationOfRevenueLineItems" xlink:to="us-gaap_ContractWithCustomerAssetNetAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerAssetAccumulatedAllowanceForCreditLoss" xlink:label="us-gaap_ContractWithCustomerAssetAccumulatedAllowanceForCreditLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ContractWithCustomerAssetNetAbstract" xlink:to="us-gaap_ContractWithCustomerAssetAccumulatedAllowanceForCreditLoss" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsGeneralInformationDetails" xlink:type="extended" xlink:title="41001 - Disclosure - Collaboration and License Agreements - General Information (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" priority="4" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementMember" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" priority="2" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_IdrxIncMember" xlink:label="bpmc_IdrxIncMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_IdrxIncMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ProteovantMember" xlink:label="bpmc_ProteovantMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_ProteovantMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ZaiLabShanghaiCoLtdMember" xlink:label="bpmc_ZaiLabShanghaiCoLtdMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_ZaiLabShanghaiCoLtdMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheMember" xlink:label="bpmc_RocheMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_RocheMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationPralsetnibAgreementMember" xlink:label="bpmc_RocheCollaborationPralsetnibAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationPralsetnibAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" xlink:label="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ClementiaMember" xlink:label="bpmc_ClementiaMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_ClementiaMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CStoneMember" xlink:label="bpmc_CStoneMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_CStoneMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:label="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RelatedPartyDomain" xlink:label="us-gaap_RelatedPartyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:to="us-gaap_RelatedPartyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ManagementMember" xlink:label="srt_ManagementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_RelatedPartyDomain" xlink:to="srt_ManagementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_DirectorMember" xlink:label="srt_DirectorMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ManagementMember" xlink:to="srt_DirectorMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementUpfrontPaymentCashPaymentReceived" xlink:label="bpmc_CollaborativeArrangementUpfrontPaymentCashPaymentReceived" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementUpfrontPaymentCashPaymentReceived" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementUpfrontPayment" xlink:label="bpmc_CollaborativeArrangementUpfrontPayment" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementUpfrontPayment" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementMilestonesPotentialContingentPayments" xlink:label="bpmc_CollaborativeArrangementMilestonesPotentialContingentPayments" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementMilestonesPotentialContingentPayments" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementMilestonesCashPaymentsReceived" xlink:label="bpmc_CollaborativeArrangementMilestonesCashPaymentsReceived" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementMilestonesCashPaymentsReceived" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementMilestonesContingentPaymentsEligibleToReceive" xlink:label="bpmc_CollaborativeArrangementMilestonesContingentPaymentsEligibleToReceive" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementMilestonesContingentPaymentsEligibleToReceive" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementMilestonesCashPaymentsReceivedAggregate" xlink:label="bpmc_CollaborativeArrangementMilestonesCashPaymentsReceivedAggregate" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementMilestonesCashPaymentsReceivedAggregate" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementOptionFeesAndMilestonesContingentPaymentsEligibleToReceive" xlink:label="bpmc_CollaborativeArrangementOptionFeesAndMilestonesContingentPaymentsEligibleToReceive" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementOptionFeesAndMilestonesContingentPaymentsEligibleToReceive" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementMilestonesAchieved" xlink:label="bpmc_CollaborativeArrangementMilestonesAchieved" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementMilestonesAchieved" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementMilestonesSpecifiedRegulatoryAndCommercializationMilestonesAchieved" xlink:label="bpmc_CollaborativeArrangementMilestonesSpecifiedRegulatoryAndCommercializationMilestonesAchieved" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementMilestonesSpecifiedRegulatoryAndCommercializationMilestonesAchieved" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementMilestonesResearchMilestonesAchieved" xlink:label="bpmc_CollaborativeArrangementMilestonesResearchMilestonesAchieved" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementMilestonesResearchMilestonesAchieved" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementPercentageOfGlobalDevelopmentCostsSharedEntity" xlink:label="bpmc_CollaborativeArrangementPercentageOfGlobalDevelopmentCostsSharedEntity" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="12" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementPercentageOfGlobalDevelopmentCostsSharedEntity" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementPercentageOfGlobalDevelopmentCostsSharedCounterparty" xlink:label="bpmc_CollaborativeArrangementPercentageOfGlobalDevelopmentCostsSharedCounterparty" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="13" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementPercentageOfGlobalDevelopmentCostsSharedCounterparty" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementInventoryPurchasedByCounterparty" xlink:label="bpmc_CollaborativeArrangementInventoryPurchasedByCounterparty" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="14" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementInventoryPurchasedByCounterparty" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementLicensedProductTermFromFirstCommercialSale" xlink:label="bpmc_CollaborativeArrangementLicensedProductTermFromFirstCommercialSale" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="15" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementLicensedProductTermFromFirstCommercialSale" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementLicenseOptionRightsNumber" xlink:label="bpmc_CollaborativeArrangementLicenseOptionRightsNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="16" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementLicenseOptionRightsNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementCollaborationProgramsWithExclusiveCommercializationRightsNumber" xlink:label="bpmc_CollaborativeArrangementCollaborationProgramsWithExclusiveCommercializationRightsNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="17" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementCollaborationProgramsWithExclusiveCommercializationRightsNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementCollaborationProgramsNumber" xlink:label="bpmc_CollaborativeArrangementCollaborationProgramsNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="18" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementCollaborationProgramsNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementCollaborationProgramsLicensedProductsCommercializationRightsCounterpartyExercisesOptionCounterpartyReceivesWorldwideExclusivityNumber" xlink:label="bpmc_CollaborativeArrangementCollaborationProgramsLicensedProductsCommercializationRightsCounterpartyExercisesOptionCounterpartyReceivesWorldwideExclusivityNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="19" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementCollaborationProgramsLicensedProductsCommercializationRightsCounterpartyExercisesOptionCounterpartyReceivesWorldwideExclusivityNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementCollaborationProgramsLicensedProductsCommercializationRightsCounterpartyExercisesOptionEntityRetainsDomesticAndCounterpartyReceivesInternationalNumber" xlink:label="bpmc_CollaborativeArrangementCollaborationProgramsLicensedProductsCommercializationRightsCounterpartyExercisesOptionEntityRetainsDomesticAndCounterpartyReceivesInternationalNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="20" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementCollaborationProgramsLicensedProductsCommercializationRightsCounterpartyExercisesOptionEntityRetainsDomesticAndCounterpartyReceivesInternationalNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriod" xlink:label="bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriod" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="21" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriod" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriodAfterOptionExerciseIfLicensedProductsHaveNotBeenCommerciallySold" xlink:label="bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriodAfterOptionExerciseIfLicensedProductsHaveNotBeenCommerciallySold" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="22" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriodAfterOptionExerciseIfLicensedProductsHaveNotBeenCommerciallySold" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriodAfterOptionExerciseIfLicensedProductsHaveBeenCommerciallySold" xlink:label="bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriodAfterOptionExerciseIfLicensedProductsHaveBeenCommerciallySold" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="23" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriodAfterOptionExerciseIfLicensedProductsHaveBeenCommerciallySold" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriodPeriodFromEffectiveDate" xlink:label="bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriodPeriodFromEffectiveDate" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="24" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriodPeriodFromEffectiveDate" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriodPeriodFromEffectiveDateGivenAfterFirstCommercialSaleOfLicensedProductInCounterpartyTerritory" xlink:label="bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriodPeriodFromEffectiveDateGivenAfterFirstCommercialSaleOfLicensedProductInCounterpartyTerritory" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="25" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriodPeriodFromEffectiveDateGivenAfterFirstCommercialSaleOfLicensedProductInCounterpartyTerritory" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriodPeriodFromEffectiveDateGivenPriorToFirstCommercialSaleOfLicensedProductInCounterpartyTerritory" xlink:label="bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriodPeriodFromEffectiveDateGivenPriorToFirstCommercialSaleOfLicensedProductInCounterpartyTerritory" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="26" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementTerminationCounterpartyWrittenNoticePeriodPeriodFromEffectiveDateGivenPriorToFirstCommercialSaleOfLicensedProductInCounterpartyTerritory" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementClinicalTrialsSharedDevelopmentCost" xlink:label="bpmc_CollaborativeArrangementClinicalTrialsSharedDevelopmentCost" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="27" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementClinicalTrialsSharedDevelopmentCost" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent" xlink:label="us-gaap_PrepaidExpenseAndOtherAssetsCurrent" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="28" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_PrepaidExpenseAndOtherAssetsCurrent" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ResearchAndDevelopmentExpense" xlink:label="us-gaap_ResearchAndDevelopmentExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="29" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ResearchAndDevelopmentExpense" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsTransactionPriceDetails" xlink:type="extended" xlink:title="41002 - Disclosure - Collaboration and License Agreements - Transaction Price (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" priority="5" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementMember" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" priority="3" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ZaiLabShanghaiCoLtdMember" xlink:label="bpmc_ZaiLabShanghaiCoLtdMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_ZaiLabShanghaiCoLtdMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheMember" xlink:label="bpmc_RocheMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_RocheMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationPralsetnibAgreementMember" xlink:label="bpmc_RocheCollaborationPralsetnibAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationPralsetnibAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" xlink:label="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ClementiaMember" xlink:label="bpmc_ClementiaMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_ClementiaMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CStoneMember" xlink:label="bpmc_CStoneMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_CStoneMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementTransactionPrice" xlink:label="bpmc_CollaborativeArrangementTransactionPrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementTransactionPrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementTransactionPriceUpfrontPayment" xlink:label="bpmc_CollaborativeArrangementTransactionPriceUpfrontPayment" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementTransactionPriceUpfrontPayment" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementTransactionPriceStockIssuedPremiumOnSaleOfStockToCounterparty" xlink:label="bpmc_CollaborativeArrangementTransactionPriceStockIssuedPremiumOnSaleOfStockToCounterparty" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementTransactionPriceStockIssuedPremiumOnSaleOfStockToCounterparty" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementTransactionPriceMilestonePaymentsReceivable" xlink:label="bpmc_CollaborativeArrangementTransactionPriceMilestonePaymentsReceivable" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementTransactionPriceMilestonePaymentsReceivable" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementTransactionPriceResearchMilestoneAchievedCashConsideration" xlink:label="bpmc_CollaborativeArrangementTransactionPriceResearchMilestoneAchievedCashConsideration" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementTransactionPriceResearchMilestoneAchievedCashConsideration" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementTransactionPricePaymentCommitmentReduction" xlink:label="bpmc_CollaborativeArrangementTransactionPricePaymentCommitmentReduction" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementTransactionPricePaymentCommitmentReduction" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementTransactionPriceReduction" xlink:label="bpmc_CollaborativeArrangementTransactionPriceReduction" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementTransactionPriceReduction" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsEquityInvestmentDetails" xlink:type="extended" xlink:title="41003 - Disclosure - Collaboration and License Agreements - Equity Investment (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementMember" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_IdrxIncMember" xlink:label="bpmc_IdrxIncMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_IdrxIncMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:label="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RelatedPartyDomain" xlink:label="us-gaap_RelatedPartyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:to="us-gaap_RelatedPartyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ManagementMember" xlink:label="srt_ManagementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_RelatedPartyDomain" xlink:to="srt_ManagementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_DirectorMember" xlink:label="srt_DirectorMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ManagementMember" xlink:to="srt_DirectorMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EquitySecuritiesFvNiAndWithoutReadilyDeterminableFairValueAbstract" xlink:label="us-gaap_EquitySecuritiesFvNiAndWithoutReadilyDeterminableFairValueAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_EquitySecuritiesFvNiAndWithoutReadilyDeterminableFairValueAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_EquitySecuritiesWithoutReadilyDeterminableFairValueLicenseAgreementSharesReceived" xlink:label="bpmc_EquitySecuritiesWithoutReadilyDeterminableFairValueLicenseAgreementSharesReceived" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_EquitySecuritiesFvNiAndWithoutReadilyDeterminableFairValueAbstract" xlink:to="bpmc_EquitySecuritiesWithoutReadilyDeterminableFairValueLicenseAgreementSharesReceived" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EquitySecuritiesWithoutReadilyDeterminableFairValueAmount" xlink:label="us-gaap_EquitySecuritiesWithoutReadilyDeterminableFairValueAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_EquitySecuritiesFvNiAndWithoutReadilyDeterminableFairValueAbstract" xlink:to="us-gaap_EquitySecuritiesWithoutReadilyDeterminableFairValueAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_EquitySecuritiesWithoutReadilyDeterminableFairValueTransactionCosts" xlink:label="bpmc_EquitySecuritiesWithoutReadilyDeterminableFairValueTransactionCosts" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_EquitySecuritiesFvNiAndWithoutReadilyDeterminableFairValueAbstract" xlink:to="bpmc_EquitySecuritiesWithoutReadilyDeterminableFairValueTransactionCosts" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsSaleOfStockDetails" xlink:type="extended" xlink:title="41004 - Disclosure - Collaboration and License Agreements - Sale of Stock (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable" xlink:label="us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SubsidiarySaleOfStockAxis" xlink:label="us-gaap_SubsidiarySaleOfStockAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable" xlink:to="us-gaap_SubsidiarySaleOfStockAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PrivatePlacementMember" xlink:label="us-gaap_PrivatePlacementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="us-gaap_PrivatePlacementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SubsidiarySaleOfStockLineItems" xlink:label="us-gaap_SubsidiarySaleOfStockLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_SubsidiarySaleOfStockLineItems" xlink:to="us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_SubsidiarySaleOfStockLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SharePrice" xlink:label="us-gaap_SharePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_SubsidiarySaleOfStockLineItems" xlink:to="us-gaap_SharePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_StockIssuedDuringPeriodValueNewIssuesPurchaseConsideration" xlink:label="bpmc_StockIssuedDuringPeriodValueNewIssuesPurchaseConsideration" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_SubsidiarySaleOfStockLineItems" xlink:to="bpmc_StockIssuedDuringPeriodValueNewIssuesPurchaseConsideration" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodValueNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_SubsidiarySaleOfStockLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodValueNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_StockIssuedDuringPeriodValueNewIssuesPremium" xlink:label="bpmc_StockIssuedDuringPeriodValueNewIssuesPremium" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_SubsidiarySaleOfStockLineItems" xlink:to="bpmc_StockIssuedDuringPeriodValueNewIssuesPremium" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsManufacturingAndResearchAndDevelopmentServicesDetails" xlink:type="extended" xlink:title="41005 - Disclosure - Collaboration and License Agreements - Manufacturing and Research and Development Services (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementMember" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CStoneMember" xlink:label="bpmc_CStoneMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_CStoneMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementManufacturingAndResearchAndDevelopmentServicesRelatedToGlobalDevelopmentActivitiesNetOfCostSharingPayments" xlink:label="bpmc_CollaborativeArrangementManufacturingAndResearchAndDevelopmentServicesRelatedToGlobalDevelopmentActivitiesNetOfCostSharingPayments" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementManufacturingAndResearchAndDevelopmentServicesRelatedToGlobalDevelopmentActivitiesNetOfCostSharingPayments" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsRevenueRecognizedDetails" xlink:type="extended" xlink:title="41006 - Disclosure - Collaboration and License Agreements - Revenue Recognized (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DisaggregationOfRevenueTable" xlink:label="us-gaap_DisaggregationOfRevenueTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_DisaggregationOfRevenueTable" xlink:to="us-gaap_TypeOfArrangementAxis" priority="2" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementMember" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_DisaggregationOfRevenueTable" xlink:to="srt_ProductOrServiceAxis" priority="2" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborationAndLicenseMember" xlink:label="bpmc_CollaborationAndLicenseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ProductsAndServicesDomain" xlink:to="bpmc_CollaborationAndLicenseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborationMember" xlink:label="bpmc_CollaborationMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_CollaborationAndLicenseMember" xlink:to="bpmc_CollaborationMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_LicenseMilestoneMember" xlink:label="bpmc_LicenseMilestoneMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_CollaborationMember" xlink:to="bpmc_LicenseMilestoneMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_TerritorySpecificActivitiesMember" xlink:label="bpmc_TerritorySpecificActivitiesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="bpmc_CollaborationMember" xlink:to="bpmc_TerritorySpecificActivitiesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_TerritorySpecificActivitiesManufacturingServicesAndRoyaltyMember" xlink:label="bpmc_TerritorySpecificActivitiesManufacturingServicesAndRoyaltyMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_TerritorySpecificActivitiesMember" xlink:to="bpmc_TerritorySpecificActivitiesManufacturingServicesAndRoyaltyMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_TerritorySpecificActivitiesManufacturingAndResearchAndDevelopmentServicesMember" xlink:label="bpmc_TerritorySpecificActivitiesManufacturingAndResearchAndDevelopmentServicesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="bpmc_TerritorySpecificActivitiesMember" xlink:to="bpmc_TerritorySpecificActivitiesManufacturingAndResearchAndDevelopmentServicesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RoyaltyMember" xlink:label="us-gaap_RoyaltyMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="bpmc_CollaborationMember" xlink:to="us-gaap_RoyaltyMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LicenseMember" xlink:label="us-gaap_LicenseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="bpmc_CollaborationAndLicenseMember" xlink:to="us-gaap_LicenseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_DisaggregationOfRevenueTable" xlink:to="srt_CounterpartyNameAxis" priority="2" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_IdrxIncMember" xlink:label="bpmc_IdrxIncMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_IdrxIncMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ZaiLabShanghaiCoLtdMember" xlink:label="bpmc_ZaiLabShanghaiCoLtdMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_ZaiLabShanghaiCoLtdMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheMember" xlink:label="bpmc_RocheMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_RocheMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationPralsetnibAgreementMember" xlink:label="bpmc_RocheCollaborationPralsetnibAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationPralsetnibAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" xlink:label="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ClementiaMember" xlink:label="bpmc_ClementiaMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_ClementiaMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CStoneMember" xlink:label="bpmc_CStoneMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_CStoneMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:label="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="4" xlink:from="us-gaap_DisaggregationOfRevenueTable" xlink:to="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RelatedPartyDomain" xlink:label="us-gaap_RelatedPartyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:to="us-gaap_RelatedPartyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ManagementMember" xlink:label="srt_ManagementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_RelatedPartyDomain" xlink:to="srt_ManagementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_DirectorMember" xlink:label="srt_DirectorMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ManagementMember" xlink:to="srt_DirectorMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="us-gaap_DisaggregationOfRevenueLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_DisaggregationOfRevenueLineItems" xlink:to="us-gaap_DisaggregationOfRevenueTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenuesAbstract" xlink:label="us-gaap_RevenuesAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DisaggregationOfRevenueLineItems" xlink:to="us-gaap_RevenuesAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_RevenuesAbstract" xlink:to="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RevenueFromContractWithCustomerIncludingAssessedTaxCumulativeRevenueCatchUp" xlink:label="bpmc_RevenueFromContractWithCustomerIncludingAssessedTaxCumulativeRevenueCatchUp" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_RevenuesAbstract" xlink:to="bpmc_RevenueFromContractWithCustomerIncludingAssessedTaxCumulativeRevenueCatchUp" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsCollaborationLossSharingDetails" xlink:type="extended" xlink:title="41007 - Disclosure - Collaboration and License Agreements - Collaboration Loss Sharing (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheMember" xlink:label="bpmc_RocheMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_RocheMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationPralsetnibAgreementMember" xlink:label="bpmc_RocheCollaborationPralsetnibAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationPralsetnibAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementMember" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborationProfitLossSharing" xlink:label="bpmc_CollaborationProfitLossSharing" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborationProfitLossSharing" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsReductionInExpensesDetails" xlink:type="extended" xlink:title="41008 - Disclosure - Collaboration and License Agreements - Reduction in Expenses (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" priority="3" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementMember" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" priority="2" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ZaiLabShanghaiCoLtdMember" xlink:label="bpmc_ZaiLabShanghaiCoLtdMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_ZaiLabShanghaiCoLtdMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheMember" xlink:label="bpmc_RocheMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_RocheMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationPralsetnibAgreementMember" xlink:label="bpmc_RocheCollaborationPralsetnibAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationPralsetnibAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementCommercializationReductionInSellingGeneralAndAdministrativeExpenses" xlink:label="bpmc_CollaborativeArrangementCommercializationReductionInSellingGeneralAndAdministrativeExpenses" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementCommercializationReductionInSellingGeneralAndAdministrativeExpenses" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementGlobalDevelopmentActivitiesReductionInResearchAndDevelopmentExpenses" xlink:label="bpmc_CollaborativeArrangementGlobalDevelopmentActivitiesReductionInResearchAndDevelopmentExpenses" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="bpmc_CollaborativeArrangementGlobalDevelopmentActivitiesReductionInResearchAndDevelopmentExpenses" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsChangeInContractWithCustomerLiabilityDetails" xlink:type="extended" xlink:title="41009 - Disclosure - Collaboration and License Agreements - Change in Contract with Customer, Liability (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementMember" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheMember" xlink:label="bpmc_RocheMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_RocheMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" xlink:label="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerAssetAndLiabilityAbstract" xlink:label="us-gaap_ContractWithCustomerAssetAndLiabilityAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerAssetAndLiabilityAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ChangeInContractWithCustomerAssetAndLiabilityAbstract" xlink:label="us-gaap_ChangeInContractWithCustomerAssetAndLiabilityAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ContractWithCustomerAssetAndLiabilityAbstract" xlink:to="us-gaap_ChangeInContractWithCustomerAssetAndLiabilityAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ChangeInContractWithCustomerLiabilityAbstract" xlink:label="us-gaap_ChangeInContractWithCustomerLiabilityAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ChangeInContractWithCustomerAssetAndLiabilityAbstract" xlink:to="us-gaap_ChangeInContractWithCustomerLiabilityAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized" xlink:label="us-gaap_ContractWithCustomerLiabilityRevenueRecognized" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ChangeInContractWithCustomerLiabilityAbstract" xlink:to="us-gaap_ContractWithCustomerLiabilityRevenueRecognized" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsContractAssetsAndLiabilitiesDetails" xlink:type="extended" xlink:title="41010 - Disclosure - Collaboration and License Agreements - Contract Assets and Liabilities (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementMember" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheMember" xlink:label="bpmc_RocheMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_RocheMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationPralsetnibAgreementMember" xlink:label="bpmc_RocheCollaborationPralsetnibAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationPralsetnibAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" xlink:label="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementPhaseIClinicalTrialsMember" xlink:label="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementPhaseIClinicalTrialsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" xlink:to="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementPhaseIClinicalTrialsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ClementiaMember" xlink:label="bpmc_ClementiaMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_ClementiaMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CStoneMember" xlink:label="bpmc_CStoneMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_CStoneMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerAssetAfterAllowanceForCreditLossClassifiedAbstract" xlink:label="us-gaap_ContractWithCustomerAssetAfterAllowanceForCreditLossClassifiedAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerAssetAfterAllowanceForCreditLossClassifiedAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccountsReceivableNetCurrent" xlink:label="us-gaap_AccountsReceivableNetCurrent" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ContractWithCustomerAssetAfterAllowanceForCreditLossClassifiedAbstract" xlink:to="us-gaap_AccountsReceivableNetCurrent" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_UnbilledReceivablesIncludingReimbursableCostsCurrent" xlink:label="bpmc_UnbilledReceivablesIncludingReimbursableCostsCurrent" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ContractWithCustomerAssetAfterAllowanceForCreditLossClassifiedAbstract" xlink:to="bpmc_UnbilledReceivablesIncludingReimbursableCostsCurrent" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerLiabilityAbstract" xlink:label="us-gaap_ContractWithCustomerLiabilityAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ContractWithCustomerLiabilityAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerLiability" xlink:label="us-gaap_ContractWithCustomerLiability" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ContractWithCustomerLiabilityAbstract" xlink:to="us-gaap_ContractWithCustomerLiability" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerLiabilityCurrent" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ContractWithCustomerLiabilityAbstract" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ContractWithCustomerLiabilityAbstract" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ExternalResearchDevelopmentAndCommercialContractCosts" xlink:label="bpmc_ExternalResearchDevelopmentAndCommercialContractCosts" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ContractWithCustomerLiabilityAbstract" xlink:to="bpmc_ExternalResearchDevelopmentAndCommercialContractCosts" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ExternalResearchDevelopmentAndCommercialContractCostsCurrent" xlink:label="bpmc_ExternalResearchDevelopmentAndCommercialContractCostsCurrent" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_ContractWithCustomerLiabilityAbstract" xlink:to="bpmc_ExternalResearchDevelopmentAndCommercialContractCostsCurrent" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ExternalResearchDevelopmentAndCommercialContractCostsNoncurrent" xlink:label="bpmc_ExternalResearchDevelopmentAndCommercialContractCostsNoncurrent" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_ContractWithCustomerLiabilityAbstract" xlink:to="bpmc_ExternalResearchDevelopmentAndCommercialContractCostsNoncurrent" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsPerformanceObligationsDetails" xlink:type="extended" xlink:title="41011 - Disclosure - Collaboration and License Agreements - Performance Obligations (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable" xlink:label="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable" xlink:to="us-gaap_TypeOfArrangementAxis" priority="3" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementMember" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable" xlink:to="srt_CounterpartyNameAxis" priority="2" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_IdrxIncMember" xlink:label="bpmc_IdrxIncMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_IdrxIncMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ZaiLabShanghaiCoLtdMember" xlink:label="bpmc_ZaiLabShanghaiCoLtdMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_ZaiLabShanghaiCoLtdMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheMember" xlink:label="bpmc_RocheMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_RocheMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationPralsetnibAgreementMember" xlink:label="bpmc_RocheCollaborationPralsetnibAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationPralsetnibAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" xlink:label="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ClementiaMember" xlink:label="bpmc_ClementiaMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_ClementiaMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CStoneMember" xlink:label="bpmc_CStoneMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_CStoneMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis" xlink:label="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable" xlink:to="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis" priority="3" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:label="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="4" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable" xlink:to="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RelatedPartyDomain" xlink:label="us-gaap_RelatedPartyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:to="us-gaap_RelatedPartyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ManagementMember" xlink:label="srt_ManagementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_RelatedPartyDomain" xlink:to="srt_ManagementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_DirectorMember" xlink:label="srt_DirectorMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ManagementMember" xlink:to="srt_DirectorMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:label="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:to="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementMaterialPromisesNumber" xlink:label="bpmc_CollaborativeArrangementMaterialPromisesNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:to="bpmc_CollaborativeArrangementMaterialPromisesNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementMaterialPromisesCombinedIntoDistinctPerformanceObligationNumber" xlink:label="bpmc_CollaborativeArrangementMaterialPromisesCombinedIntoDistinctPerformanceObligationNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:to="bpmc_CollaborativeArrangementMaterialPromisesCombinedIntoDistinctPerformanceObligationNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementMaterialPromisesManufacturingActivitiesTerm" xlink:label="bpmc_CollaborativeArrangementMaterialPromisesManufacturingActivitiesTerm" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:to="bpmc_CollaborativeArrangementMaterialPromisesManufacturingActivitiesTerm" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementMaterialComponentsNumber" xlink:label="bpmc_CollaborativeArrangementMaterialComponentsNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:to="bpmc_CollaborativeArrangementMaterialComponentsNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RevenuePerformanceObligationPerformanceObligationsNumber" xlink:label="bpmc_RevenuePerformanceObligationPerformanceObligationsNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:to="bpmc_RevenuePerformanceObligationPerformanceObligationsNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1" xlink:label="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:to="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsPerformanceObligationsDefaultDetails" xlink:type="extended" xlink:title="41011 - Disclosure - Collaboration and License Agreements - Performance Obligations Default (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable" xlink:label="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable" xlink:to="us-gaap_TypeOfArrangementAxis" priority="3" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementMember" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable" xlink:to="srt_CounterpartyNameAxis" priority="2" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_IdrxIncMember" xlink:label="bpmc_IdrxIncMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_IdrxIncMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ZaiLabShanghaiCoLtdMember" xlink:label="bpmc_ZaiLabShanghaiCoLtdMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_ZaiLabShanghaiCoLtdMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheMember" xlink:label="bpmc_RocheMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_RocheMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationPralsetnibAgreementMember" xlink:label="bpmc_RocheCollaborationPralsetnibAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationPralsetnibAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" xlink:label="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="bpmc_RocheMember" xlink:to="bpmc_RocheCollaborationAndLicenseImmunotherapyAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ClementiaMember" xlink:label="bpmc_ClementiaMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_ClementiaMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CStoneMember" xlink:label="bpmc_CStoneMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_CStoneMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:label="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="4" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable" xlink:to="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RelatedPartyDomain" xlink:label="us-gaap_RelatedPartyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:to="us-gaap_RelatedPartyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ManagementMember" xlink:label="srt_ManagementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_RelatedPartyDomain" xlink:to="srt_ManagementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_DirectorMember" xlink:label="srt_DirectorMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ManagementMember" xlink:to="srt_DirectorMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:label="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:to="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementMaterialPromisesNumber" xlink:label="bpmc_CollaborativeArrangementMaterialPromisesNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:to="bpmc_CollaborativeArrangementMaterialPromisesNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementMaterialPromisesCombinedIntoDistinctPerformanceObligationNumber" xlink:label="bpmc_CollaborativeArrangementMaterialPromisesCombinedIntoDistinctPerformanceObligationNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:to="bpmc_CollaborativeArrangementMaterialPromisesCombinedIntoDistinctPerformanceObligationNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementMaterialPromisesManufacturingActivitiesTerm" xlink:label="bpmc_CollaborativeArrangementMaterialPromisesManufacturingActivitiesTerm" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:to="bpmc_CollaborativeArrangementMaterialPromisesManufacturingActivitiesTerm" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborativeArrangementMaterialComponentsNumber" xlink:label="bpmc_CollaborativeArrangementMaterialComponentsNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:to="bpmc_CollaborativeArrangementMaterialComponentsNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RevenuePerformanceObligationPerformanceObligationsNumber" xlink:label="bpmc_RevenuePerformanceObligationPerformanceObligationsNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:to="bpmc_RevenuePerformanceObligationPerformanceObligationsNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1" xlink:label="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems" xlink:to="us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensation2015StockOptionAndIncentivePlanDetails" xlink:type="extended" xlink:title="41101 - Disclosure - Stock-based Compensation - 2015 Stock Option and Incentive Plan (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PlanNameAxis" xlink:label="us-gaap_PlanNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_PlanNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PlanNameDomain" xlink:label="us-gaap_PlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_PlanNameAxis" xlink:to="us-gaap_PlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_StockOptionAndIncentivePlan2015Member" xlink:label="bpmc_StockOptionAndIncentivePlan2015Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_PlanNameDomain" xlink:to="bpmc_StockOptionAndIncentivePlan2015Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfAdditionalSharesAuthorized" xlink:label="bpmc_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfAdditionalSharesAuthorized" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="bpmc_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfAdditionalSharesAuthorized" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensation2020InducementPlanDetails" xlink:type="extended" xlink:title="41102 - Disclosure - Stock-based Compensation - 2020 Inducement Plan (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PlanNameAxis" xlink:label="us-gaap_PlanNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_PlanNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PlanNameDomain" xlink:label="us-gaap_PlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_PlanNameAxis" xlink:to="us-gaap_PlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_InducementPlan2020Member" xlink:label="bpmc_InducementPlan2020Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_PlanNameDomain" xlink:to="bpmc_InducementPlan2020Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensationUnrecognizedCompensationCostsDetails" xlink:type="extended" xlink:title="41104 - Disclosure - Stock-based Compensation - Unrecognized Compensation Costs (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_AwardTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RestrictedStockUnitsRSUMember" xlink:label="us-gaap_RestrictedStockUnitsRSUMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_RestrictedStockUnitsRSUMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensationRestrictedStockUnitsActivityDetails" xlink:type="extended" xlink:title="41105 - Disclosure - Stock-based Compensation - Restricted Stock Units - Activity (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_AwardTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RestrictedStockUnitsRSUMember" xlink:label="us-gaap_RestrictedStockUnitsRSUMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_RestrictedStockUnitsRSUMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensationEmployeeStockPurchasePlanDetails" xlink:type="extended" xlink:title="41106 - Disclosure - Stock-based Compensation - Employee Stock Purchase Plan (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_AwardTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeStockMember" xlink:label="us-gaap_EmployeeStockMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance" xlink:label="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_AnnualCumulativeIncreasePercentageOfNumberOfShareOfCommonStockIssuedAndOutstanding" xlink:label="bpmc_AnnualCumulativeIncreasePercentageOfNumberOfShareOfCommonStockIssuedAndOutstanding" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="bpmc_AnnualCumulativeIncreasePercentageOfNumberOfShareOfCommonStockIssuedAndOutstanding" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CommonStockIncreaseCapitalSharesReservedForFutureIssuance" xlink:label="bpmc_CommonStockIncreaseCapitalSharesReservedForFutureIssuance" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="bpmc_CommonStockIncreaseCapitalSharesReservedForFutureIssuance" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensationStockBasedCompensationExpenseByTypeDetails" xlink:type="extended" xlink:title="41108 - Disclosure - Stock-based Compensation - Stock-based Compensation Expense - By Type (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:label="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:to="us-gaap_AwardTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="us-gaap_EmployeeStockOptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RestrictedStockUnitsRSUMember" xlink:label="us-gaap_RestrictedStockUnitsRSUMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_RestrictedStockUnitsRSUMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeStockMember" xlink:label="us-gaap_EmployeeStockMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_EmployeeStockMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationAggregateDisclosuresAbstract" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationAggregateDisclosuresAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationAggregateDisclosuresAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_EmployeeServiceShareBasedCompensationAggregateDisclosuresAbstract" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_EmployeeServiceShareBasedCompensationAggregateDisclosuresAbstract" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_EmployeeServiceShareBasedCompensationAggregateDisclosuresAbstract" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensationStockBasedCompensationExpenseByClassificationDetails" xlink:type="extended" xlink:title="41109 - Disclosure - Stock-based Compensation - Stock-based Compensation Expense - By Classification (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:label="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="us-gaap_IncomeStatementLocationAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:to="us-gaap_IncomeStatementLocationAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ResearchAndDevelopmentExpenseMember" xlink:label="us-gaap_ResearchAndDevelopmentExpenseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_ResearchAndDevelopmentExpenseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpensesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpensesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_GeneralAndAdministrativeExpenseMember" xlink:label="us-gaap_GeneralAndAdministrativeExpenseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_SellingGeneralAndAdministrativeExpensesMember" xlink:to="us-gaap_GeneralAndAdministrativeExpenseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationAggregateDisclosuresAbstract" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationAggregateDisclosuresAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationAggregateDisclosuresAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_EmployeeServiceShareBasedCompensationAggregateDisclosuresAbstract" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureNetLossPerShareDetails" xlink:type="extended" xlink:title="41201 - Disclosure - Net Loss Per Share (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" xlink:label="us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" xlink:to="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" priority="2" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AntidilutiveSecuritiesNameDomain" xlink:label="us-gaap_AntidilutiveSecuritiesNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" xlink:to="us-gaap_AntidilutiveSecuritiesNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="us-gaap_EmployeeStockOptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_AntidilutiveSecuritiesNameDomain" xlink:to="us-gaap_EmployeeStockOptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RestrictedStockUnitsRSUMember" xlink:label="us-gaap_RestrictedStockUnitsRSUMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_AntidilutiveSecuritiesNameDomain" xlink:to="us-gaap_RestrictedStockUnitsRSUMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeStockMember" xlink:label="us-gaap_EmployeeStockMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_AntidilutiveSecuritiesNameDomain" xlink:to="us-gaap_EmployeeStockMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" xlink:to="us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EarningsPerShareDilutedOtherDisclosuresAbstract" xlink:label="us-gaap_EarningsPerShareDilutedOtherDisclosuresAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" xlink:to="us-gaap_EarningsPerShareDilutedOtherDisclosuresAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_EarningsPerShareDilutedOtherDisclosuresAbstract" xlink:to="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureIncomeTaxesFinancingArrangementsDetails" xlink:type="extended" xlink:title="41301 - Disclosure - Income Taxes - Financing Arrangements (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentTable" xlink:label="us-gaap_DebtInstrumentTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongtermDebtTypeAxis" xlink:label="us-gaap_LongtermDebtTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_DebtInstrumentTable" xlink:to="us-gaap_LongtermDebtTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongtermDebtTypeDomain" xlink:label="us-gaap_LongtermDebtTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_LongtermDebtTypeAxis" xlink:to="us-gaap_LongtermDebtTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SaleOfFutureRoyaltiesAndRevenuesMember" xlink:label="bpmc_SaleOfFutureRoyaltiesAndRevenuesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_LongtermDebtTypeDomain" xlink:to="bpmc_SaleOfFutureRoyaltiesAndRevenuesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentAxis" xlink:label="us-gaap_DebtInstrumentAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_DebtInstrumentTable" xlink:to="us-gaap_DebtInstrumentAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="us-gaap_DebtInstrumentNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_RoyaltyPharmaRoyaltyPurchaseAgreementMember" xlink:label="bpmc_RoyaltyPharmaRoyaltyPurchaseAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="bpmc_RoyaltyPharmaRoyaltyPurchaseAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFinancingArrangementsMember" xlink:label="bpmc_SixthStreetPartnersFinancingArrangementsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentNameDomain" xlink:to="bpmc_SixthStreetPartnersFinancingArrangementsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_SixthStreetPartnersFutureRevenuePurchaseAgreementMember" xlink:label="bpmc_SixthStreetPartnersFutureRevenuePurchaseAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_SixthStreetPartnersFinancingArrangementsMember" xlink:to="bpmc_SixthStreetPartnersFutureRevenuePurchaseAgreementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentLineItems" xlink:label="us-gaap_DebtInstrumentLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_DebtInstrumentTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentsAbstract" xlink:label="us-gaap_DebtInstrumentsAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_DebtInstrumentsAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentIssuanceDate1" xlink:label="us-gaap_DebtInstrumentIssuanceDate1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_DebtInstrumentsAbstract" xlink:to="us-gaap_DebtInstrumentIssuanceDate1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromIssuanceOfLongTermDebtAbstract" xlink:label="us-gaap_ProceedsFromIssuanceOfLongTermDebtAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_DebtInstrumentLineItems" xlink:to="us-gaap_ProceedsFromIssuanceOfLongTermDebtAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromIssuanceOfLongTermDebt" xlink:label="us-gaap_ProceedsFromIssuanceOfLongTermDebt" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ProceedsFromIssuanceOfLongTermDebtAbstract" xlink:to="us-gaap_ProceedsFromIssuanceOfLongTermDebt" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureIncomeTaxesEquityInvestmentDetails" xlink:type="extended" xlink:title="41302 - Disclosure - Income Taxes - Equity Investment (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_TypeOfArrangementAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementMember" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductOrServiceAxis" xlink:label="srt_ProductOrServiceAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_ProductOrServiceAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductsAndServicesDomain" xlink:label="srt_ProductsAndServicesDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_ProductOrServiceAxis" xlink:to="srt_ProductsAndServicesDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_CollaborationMember" xlink:label="bpmc_CollaborationMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ProductsAndServicesDomain" xlink:to="bpmc_CollaborationMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LicenseMember" xlink:label="us-gaap_LicenseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="bpmc_CollaborationMember" xlink:to="us-gaap_LicenseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="srt_CounterpartyNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_IdrxIncMember" xlink:label="bpmc_IdrxIncMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_IdrxIncMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:label="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="4" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RelatedPartyDomain" xlink:label="us-gaap_RelatedPartyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:to="us-gaap_RelatedPartyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ManagementMember" xlink:label="srt_ManagementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_RelatedPartyDomain" xlink:to="srt_ManagementMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_DirectorMember" xlink:label="srt_DirectorMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_ManagementMember" xlink:to="srt_DirectorMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EquitySecuritiesFvNiAndWithoutReadilyDeterminableFairValueAbstract" xlink:label="us-gaap_EquitySecuritiesFvNiAndWithoutReadilyDeterminableFairValueAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_EquitySecuritiesFvNiAndWithoutReadilyDeterminableFairValueAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_EquitySecuritiesWithoutReadilyDeterminableFairValueLicenseAgreementSharesReceived" xlink:label="bpmc_EquitySecuritiesWithoutReadilyDeterminableFairValueLicenseAgreementSharesReceived" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_EquitySecuritiesFvNiAndWithoutReadilyDeterminableFairValueAbstract" xlink:to="bpmc_EquitySecuritiesWithoutReadilyDeterminableFairValueLicenseAgreementSharesReceived" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenuesAbstract" xlink:label="us-gaap_RevenuesAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_RevenuesAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_RevenuesAbstract" xlink:to="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCommitmentsAndContingenciesPurchaseCommitmentsDetails" xlink:type="extended" xlink:title="41501 - Disclosure - Commitments and Contingencies - Purchase Commitments (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_UnrecordedUnconditionalPurchaseObligationTable" xlink:label="us-gaap_UnrecordedUnconditionalPurchaseObligationTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_CounterpartyNameAxis" xlink:label="srt_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_UnrecordedUnconditionalPurchaseObligationTable" xlink:to="srt_CounterpartyNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RepurchaseAgreementCounterpartyNameDomain" xlink:label="srt_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="srt_CounterpartyNameAxis" xlink:to="srt_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_ManufacturingAgreementOctober2020Member" xlink:label="bpmc_ManufacturingAgreementOctober2020Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="srt_RepurchaseAgreementCounterpartyNameDomain" xlink:to="bpmc_ManufacturingAgreementOctober2020Member" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_UnrecordedUnconditionalPurchaseObligationLineItems" xlink:label="us-gaap_UnrecordedUnconditionalPurchaseObligationLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_UnrecordedUnconditionalPurchaseObligationLineItems" xlink:to="us-gaap_UnrecordedUnconditionalPurchaseObligationTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_UnconditionalPurchaseObligationsExcludingCapitalStockRedemptionsAbstract" xlink:label="us-gaap_UnconditionalPurchaseObligationsExcludingCapitalStockRedemptionsAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_UnrecordedUnconditionalPurchaseObligationLineItems" xlink:to="us-gaap_UnconditionalPurchaseObligationsExcludingCapitalStockRedemptionsAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="bpmc-20220930.xsd#bpmc_UnrecordedUnconditionalPurchaseObligationPeriodIncreaseDecrease" xlink:label="bpmc_UnrecordedUnconditionalPurchaseObligationPeriodIncreaseDecrease" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_UnconditionalPurchaseObligationsExcludingCapitalStockRedemptionsAbstract" xlink:to="bpmc_UnrecordedUnconditionalPurchaseObligationPeriodIncreaseDecrease" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCommitmentsAndContingenciesIndemnificationAgreementsDetails" xlink:type="extended" xlink:title="41502 - Disclosure - Commitments and Contingencies - Indemnification Agreements (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LossContingenciesTable" xlink:label="us-gaap_LossContingenciesTable" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LossContingenciesByNatureOfContingencyAxis" xlink:label="us-gaap_LossContingenciesByNatureOfContingencyAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_LossContingenciesTable" xlink:to="us-gaap_LossContingenciesByNatureOfContingencyAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LossContingencyNatureDomain" xlink:label="us-gaap_LossContingencyNatureDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_LossContingenciesByNatureOfContingencyAxis" xlink:to="us-gaap_LossContingencyNatureDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_GuaranteeObligationsMember" xlink:label="us-gaap_GuaranteeObligationsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_LossContingencyNatureDomain" xlink:to="us-gaap_GuaranteeObligationsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IndemnificationGuaranteeMember" xlink:label="us-gaap_IndemnificationGuaranteeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_GuaranteeObligationsMember" xlink:to="us-gaap_IndemnificationGuaranteeMember" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LossContingenciesLineItems" xlink:label="us-gaap_LossContingenciesLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_LossContingenciesLineItems" xlink:to="us-gaap_LossContingenciesTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LossContingencyAccrualDisclosuresAbstract" xlink:label="us-gaap_LossContingencyAccrualDisclosuresAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_LossContingenciesLineItems" xlink:to="us-gaap_LossContingencyAccrualDisclosuresAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LossContingencyAccrualAtCarryingValue" xlink:label="us-gaap_LossContingencyAccrualAtCarryingValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_LossContingencyAccrualDisclosuresAbstract" xlink:to="us-gaap_LossContingencyAccrualAtCarryingValue" priority="1" use="optional" />
  </definitionLink>
</link:linkbase>
