<?xml version="1.0" encoding="us-ascii"?>
<!--XBRL document created with Toppan Merrill Bridge  9.6.7713.40453 -->
<!--Based on XBRL 2.1-->
<!--Created on: 4/29/2021 8:17:22 PM-->
<!--Modified on: 4/29/2021 8:17:22 PM-->
<linkbase xmlns="http://www.xbrl.org/2003/linkbase" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xlink="http://www.w3.org/1999/xlink" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <roleRef xlink:type="simple" xlink:href="bpmc-20210331.xsd#StatementCondensedConsolidatedBalanceSheets" roleURI="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedBalanceSheets" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20210331.xsd#StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss" roleURI="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20210331.xsd#StatementCondensedConsolidatedStatementsOfCashFlows" roleURI="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedStatementsOfCashFlows" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20210331.xsd#StatementCondensedConsolidatedStatementsOfCashFlowsParenthetical" roleURI="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedStatementsOfCashFlowsParenthetical" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20210331.xsd#DisclosureMarketableSecuritiesTabularDisclosureDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureMarketableSecuritiesTabularDisclosureDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20210331.xsd#DisclosureFairValueOfFinancialInstrumentsDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureFairValueOfFinancialInstrumentsDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20210331.xsd#DisclosureInventoryCapitalizedDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureInventoryCapitalizedDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20210331.xsd#DisclosureInventoryBalanceSheetClassificationDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureInventoryBalanceSheetClassificationDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20210331.xsd#DisclosurePropertyAndEquipmentNetPropertyAndEquipmentAndRelatedAccumulatedDepreciationDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosurePropertyAndEquipmentNetPropertyAndEquipmentAndRelatedAccumulatedDepreciationDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20210331.xsd#DisclosureAccruedExpensesDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureAccruedExpensesDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20210331.xsd#DisclosureCollaborationAndLicenseAgreementsGeneralInformationDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsGeneralInformationDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20210331.xsd#DisclosureCollaborationAndLicenseAgreementsTransactionPriceDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsTransactionPriceDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20210331.xsd#DisclosureCollaborationAndLicenseAgreementsSaleOfStockDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsSaleOfStockDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20210331.xsd#DisclosureStockBasedCompensationStockBasedCompensationExpenseByTypeDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureStockBasedCompensationStockBasedCompensationExpenseByTypeDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20210331.xsd#DisclosureLeasesComponentsOfLeaseExpenseDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureLeasesComponentsOfLeaseExpenseDetails" />
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedBalanceSheets" xlink:type="extended" xlink:title="00100 - Statement - Condensed Consolidated Balance Sheets">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockholdersEquity" xlink:label="us-gaap_StockholdersEquity_637553242402327717" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_StockholdersEquity_637553242402327717" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PreferredStockValueOutstanding" xlink:label="us-gaap_PreferredStockValueOutstanding_637553242402327717" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_637553242402327717" xlink:to="us-gaap_PreferredStockValueOutstanding_637553242402327717" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CommonStockValue" xlink:label="us-gaap_CommonStockValue_637553242402327717" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_637553242402327717" xlink:to="us-gaap_CommonStockValue_637553242402327717" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AdditionalPaidInCapital" xlink:label="us-gaap_AdditionalPaidInCapital_637553242402327717" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_637553242402327717" xlink:to="us-gaap_AdditionalPaidInCapital_637553242402327717" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_637553242402327717" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_637553242402327717" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_637553242402327717" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit_637553242402327717" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_637553242402327717" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit_637553242402327717" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Liabilities" xlink:label="us-gaap_Liabilities_637553242402327717" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_Liabilities_637553242402327717" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:label="us-gaap_LiabilitiesCurrent_637553242402327717" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_637553242402327717" xlink:to="us-gaap_LiabilitiesCurrent_637553242402327717" order="1" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccountsPayableCurrent" xlink:label="us-gaap_AccountsPayableCurrent_637553242402327717" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_637553242402327717" xlink:to="us-gaap_AccountsPayableCurrent_637553242402327717" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="us-gaap_AccruedLiabilitiesCurrent_637553242402327717" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_637553242402327717" xlink:to="us-gaap_AccruedLiabilitiesCurrent_637553242402327717" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent_637553242402337706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_637553242402327717" xlink:to="us-gaap_OperatingLeaseLiabilityCurrent_637553242402337706" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractWithCustomerLiabilityCurrent" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_637553242402337706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_637553242402327717" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_637553242402337706" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:label="us-gaap_OperatingLeaseLiabilityNoncurrent_637553242402337706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_637553242402327717" xlink:to="us-gaap_OperatingLeaseLiabilityNoncurrent_637553242402337706" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent_637553242402337706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_637553242402327717" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent_637553242402337706" order="3" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherLiabilitiesNoncurrent" xlink:label="us-gaap_OtherLiabilitiesNoncurrent_637553242402337706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_637553242402327717" xlink:to="us-gaap_OtherLiabilitiesNoncurrent_637553242402337706" order="4" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Assets" xlink:label="us-gaap_Assets" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AssetsCurrent" xlink:label="us-gaap_AssetsCurrent_637553242402337706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_AssetsCurrent_637553242402337706" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue_637553242402347708" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637553242402337706" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue_637553242402347708" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_UnbilledReceivablesIncludingReimbursableCostsCurrent" xlink:label="bpmc_UnbilledReceivablesIncludingReimbursableCostsCurrent_637553242402347708" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637553242402337706" xlink:to="bpmc_UnbilledReceivablesIncludingReimbursableCostsCurrent_637553242402347708" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_637553242402347708" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637553242402337706" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_637553242402347708" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InventoryNet" xlink:label="us-gaap_InventoryNet_637553242402347708" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637553242402337706" xlink:to="us-gaap_InventoryNet_637553242402347708" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent" xlink:label="us-gaap_PrepaidExpenseAndOtherAssetsCurrent_637553242402347708" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637553242402337706" xlink:to="us-gaap_PrepaidExpenseAndOtherAssetsCurrent_637553242402347708" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccountsReceivableNetCurrent" xlink:label="us-gaap_AccountsReceivableNetCurrent_637553242402347708" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637553242402337706" xlink:to="us-gaap_AccountsReceivableNetCurrent_637553242402347708" order="6" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent_637553242402347708" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent_637553242402347708" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_637553242402357703" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_PropertyPlantAndEquipmentNet_637553242402357703" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAsset" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset_637553242402357703" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset_637553242402357703" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherAssetsNoncurrent" xlink:label="us-gaap_OtherAssetsNoncurrent_637553242402357703" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_OtherAssetsNoncurrent_637553242402357703" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RestrictedCashNoncurrent" xlink:label="us-gaap_RestrictedCashNoncurrent_637553242402357703" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_RestrictedCashNoncurrent_637553242402357703" order="6" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss" xlink:type="extended" xlink:title="00200 - Statement - Condensed Consolidated Statements of Operations and Comprehensive Loss">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss_637553242402357703" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_NetIncomeLoss_637553242402357703" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_637553242402367706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss_637553242402357703" xlink:to="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_637553242402367706" order="1" use="optional" weight="1" priority="4" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CostsAndExpenses" xlink:label="us-gaap_CostsAndExpenses_637553242402367706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss_637553242402357703" xlink:to="us-gaap_CostsAndExpenses_637553242402367706" order="2" use="optional" weight="-1" priority="4" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="us-gaap_CostOfGoodsAndServicesSold_637553242402367706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CostsAndExpenses_637553242402367706" xlink:to="us-gaap_CostOfGoodsAndServicesSold_637553242402367706" order="1" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ResearchAndDevelopmentExpense" xlink:label="us-gaap_ResearchAndDevelopmentExpense_637553242402367706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CostsAndExpenses_637553242402367706" xlink:to="us-gaap_ResearchAndDevelopmentExpense_637553242402367706" order="2" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpense" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpense_637553242402367706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CostsAndExpenses_637553242402367706" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpense_637553242402367706" order="3" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NonoperatingIncomeExpense" xlink:label="us-gaap_NonoperatingIncomeExpense_637553242402367706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss_637553242402357703" xlink:to="us-gaap_NonoperatingIncomeExpense_637553242402367706" order="3" use="optional" weight="1" priority="4" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="us-gaap_OtherNonoperatingIncomeExpense_637553242402367706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NonoperatingIncomeExpense_637553242402367706" xlink:to="us-gaap_OtherNonoperatingIncomeExpense_637553242402367706" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InterestIncomeExpenseNet" xlink:label="us-gaap_InterestIncomeExpenseNet_637553242402367706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NonoperatingIncomeExpense_637553242402367706" xlink:to="us-gaap_InterestIncomeExpenseNet_637553242402367706" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax" xlink:label="us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax_637553242402367706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax_637553242402367706" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:label="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_637553242402367706" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_637553242402367706" order="3" use="optional" weight="1" priority="3" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedStatementsOfCashFlows" xlink:type="extended" xlink:title="00400 - Statement - Condensed Consolidated Statements of Cash Flows">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" order="1" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProfitLoss" xlink:label="us-gaap_ProfitLoss_637553242402377705" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" xlink:to="us-gaap_ProfitLoss_637553242402377705" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DepreciationDepletionAndAmortization" xlink:label="us-gaap_DepreciationDepletionAndAmortization_637553242402377705" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" xlink:to="us-gaap_DepreciationDepletionAndAmortization_637553242402377705" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_LeaseRightOfUseAssetAmortization" xlink:label="bpmc_LeaseRightOfUseAssetAmortization_637553242402377705" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" xlink:to="bpmc_LeaseRightOfUseAssetAmortization_637553242402377705" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherOperatingActivitiesCashFlowStatement" xlink:label="us-gaap_OtherOperatingActivitiesCashFlowStatement_637553242402377705" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" xlink:to="us-gaap_OtherOperatingActivitiesCashFlowStatement_637553242402377705" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayable" xlink:label="us-gaap_IncreaseDecreaseInAccountsPayable_637553242402377705" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" xlink:to="us-gaap_IncreaseDecreaseInAccountsPayable_637553242402377705" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_IncreaseDecreaseInCustomerAssets" xlink:label="bpmc_IncreaseDecreaseInCustomerAssets_637553242402377705" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" xlink:to="bpmc_IncreaseDecreaseInCustomerAssets_637553242402377705" order="6" use="optional" weight="-1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInInventories" xlink:label="us-gaap_IncreaseDecreaseInInventories_637553242402387705" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" xlink:to="us-gaap_IncreaseDecreaseInInventories_637553242402387705" order="7" use="optional" weight="-1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets" xlink:label="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_637553242402387705" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" xlink:to="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_637553242402387705" order="8" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensation" xlink:label="us-gaap_ShareBasedCompensation_637553242402387705" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" xlink:to="us-gaap_ShareBasedCompensation_637553242402387705" order="9" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsReceivable" xlink:label="us-gaap_IncreaseDecreaseInAccountsReceivable_637553242402387705" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" xlink:to="us-gaap_IncreaseDecreaseInAccountsReceivable_637553242402387705" order="10" use="optional" weight="-1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInOtherNoncurrentAssets" xlink:label="us-gaap_IncreaseDecreaseInOtherNoncurrentAssets_637553242402387705" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" xlink:to="us-gaap_IncreaseDecreaseInOtherNoncurrentAssets_637553242402387705" order="11" use="optional" weight="-1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInAccruedLiabilities" xlink:label="us-gaap_IncreaseDecreaseInAccruedLiabilities_637553242402387705" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" xlink:to="us-gaap_IncreaseDecreaseInAccruedLiabilities_637553242402387705" order="12" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerLiability" xlink:label="us-gaap_IncreaseDecreaseInContractWithCustomerLiability_637553242402387705" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" xlink:to="us-gaap_IncreaseDecreaseInContractWithCustomerLiability_637553242402387705" order="13" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_IncreaseDecreaseInOperatingLeaseLiabilities" xlink:label="bpmc_IncreaseDecreaseInOperatingLeaseLiabilities_637553242402387705" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637553242402377705" xlink:to="bpmc_IncreaseDecreaseInOperatingLeaseLiabilities_637553242402387705" order="14" use="optional" weight="1" priority="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities_637553242402397701" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities_637553242402397701" order="2" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_ProceedsFromIssuanceOfCommonStockNetOfUnderwritingDiscountsCommissionsAndOfferingExpenses" xlink:label="bpmc_ProceedsFromIssuanceOfCommonStockNetOfUnderwritingDiscountsCommissionsAndOfferingExpenses_637553242402397701" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_637553242402397701" xlink:to="bpmc_ProceedsFromIssuanceOfCommonStockNetOfUnderwritingDiscountsCommissionsAndOfferingExpenses_637553242402397701" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_NetProceedsFromStockOptionExercisesAndEmployeeStockPurchasePlan" xlink:label="bpmc_NetProceedsFromStockOptionExercisesAndEmployeeStockPurchasePlan_637553242402397701" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_637553242402397701" xlink:to="bpmc_NetProceedsFromStockOptionExercisesAndEmployeeStockPurchasePlan_637553242402397701" order="2" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities_637553242402397701" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities_637553242402397701" order="3" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_637553242402397701" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_637553242402397701" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_637553242402397701" order="1" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:label="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_637553242402397701" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_637553242402397701" xlink:to="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_637553242402397701" order="2" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities" xlink:label="us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities_637553242402397701" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_637553242402397701" xlink:to="us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities_637553242402397701" order="3" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedStatementsOfCashFlowsParenthetical" xlink:type="extended" xlink:title="00405 - Statement - Condensed Consolidated Statements of Cash Flows (Parenthetical)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue_637553242402407714" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue_637553242402407714" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RestrictedCashNoncurrent" xlink:label="us-gaap_RestrictedCashNoncurrent_637553242402407714" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:to="us-gaap_RestrictedCashNoncurrent_637553242402407714" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureMarketableSecuritiesTabularDisclosureDetails" xlink:type="extended" xlink:title="40301 - Disclosure - Marketable Securities - Tabular Disclosure (Details)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_636760594423441400" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_637553242402407714" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_636760594423441400" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_637553242402407714" order="1" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_637553242402407714" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_636760594423441400" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_637553242402407714" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities_637553242402407714" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_636760594423441400" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities_637553242402407714" order="3" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureFairValueOfFinancialInstrumentsDetails" xlink:type="extended" xlink:title="40401 - Disclosure - Fair Value of Financial Instruments (Details)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AssetsFairValueDisclosure" xlink:label="us-gaap_AssetsFairValueDisclosure" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities_637553242402407714" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsFairValueDisclosure" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities_637553242402407714" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure" xlink:label="us-gaap_CashAndCashEquivalentsFairValueDisclosure_637553242402417711" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsFairValueDisclosure" xlink:to="us-gaap_CashAndCashEquivalentsFairValueDisclosure_637553242402417711" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureInventoryCapitalizedDetails" xlink:type="extended" xlink:title="40601 - Disclosure - Inventory - Capitalized (Details)">
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_InventoryCurrentAndNoncurrentNet" xlink:label="bpmc_InventoryCurrentAndNoncurrentNet" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_InventoryCurrentAndNoncurrentWorkInProcessNetOfReserves" xlink:label="bpmc_InventoryCurrentAndNoncurrentWorkInProcessNetOfReserves_637553242402417711" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_InventoryCurrentAndNoncurrentNet" xlink:to="bpmc_InventoryCurrentAndNoncurrentWorkInProcessNetOfReserves_637553242402417711" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_InventoryCurrentAndNoncurrentFinishedGoodsNetOfReserves" xlink:label="bpmc_InventoryCurrentAndNoncurrentFinishedGoodsNetOfReserves_637553242402417711" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_InventoryCurrentAndNoncurrentNet" xlink:to="bpmc_InventoryCurrentAndNoncurrentFinishedGoodsNetOfReserves_637553242402417711" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureInventoryBalanceSheetClassificationDetails" xlink:type="extended" xlink:title="40602 - Disclosure - Inventory - Balance Sheet Classification (Details)">
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_InventoryCurrentAndNoncurrentNet" xlink:label="bpmc_InventoryCurrentAndNoncurrentNet" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InventoryNet" xlink:label="us-gaap_InventoryNet_637553242402417711" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_InventoryCurrentAndNoncurrentNet" xlink:to="us-gaap_InventoryNet_637553242402417711" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InventoryNoncurrent" xlink:label="us-gaap_InventoryNoncurrent_637553242402417711" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_InventoryCurrentAndNoncurrentNet" xlink:to="us-gaap_InventoryNoncurrent_637553242402417711" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosurePropertyAndEquipmentNetPropertyAndEquipmentAndRelatedAccumulatedDepreciationDetails" xlink:type="extended" xlink:title="40802 - Disclosure - Property and Equipment, Net - Property and Equipment and Related Accumulated Depreciation (Details)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_635902680813050767" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment" xlink:label="us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_637553242402427710" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_PropertyPlantAndEquipmentNet_635902680813050767" xlink:to="us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_637553242402427710" order="1" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentGross" xlink:label="us-gaap_PropertyPlantAndEquipmentGross_637553242402427710" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_PropertyPlantAndEquipmentNet_635902680813050767" xlink:to="us-gaap_PropertyPlantAndEquipmentGross_637553242402427710" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureAccruedExpensesDetails" xlink:type="extended" xlink:title="40901 - Disclosure - Accrued Expenses (Details)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="us-gaap_AccruedLiabilitiesCurrent" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_ExternalResearchDevelopmentAndCommercialContractCostsCurrent" xlink:label="bpmc_ExternalResearchDevelopmentAndCommercialContractCostsCurrent_637553242402427710" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="bpmc_ExternalResearchDevelopmentAndCommercialContractCostsCurrent_637553242402427710" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_AccruedContractWithCustomerAssetAccumulatedAllowanceForCreditLoss" xlink:label="bpmc_AccruedContractWithCustomerAssetAccumulatedAllowanceForCreditLoss_637553242402427710" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="bpmc_AccruedContractWithCustomerAssetAccumulatedAllowanceForCreditLoss_637553242402427710" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:label="us-gaap_EmployeeRelatedLiabilitiesCurrent_637553242402427710" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_EmployeeRelatedLiabilitiesCurrent_637553242402427710" order="3" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccruedProfessionalFeesCurrent" xlink:label="us-gaap_AccruedProfessionalFeesCurrent_637553242402427710" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_AccruedProfessionalFeesCurrent_637553242402427710" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherAccruedLiabilitiesCurrent" xlink:label="us-gaap_OtherAccruedLiabilitiesCurrent_637553242402427710" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AccruedLiabilitiesCurrent" xlink:to="us-gaap_OtherAccruedLiabilitiesCurrent_637553242402427710" order="5" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsGeneralInformationDetails" xlink:type="extended" xlink:title="41001 - Disclosure - Collaboration and License Agreements - General Information (Details)">
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_CollaborativeArrangementMilestonesContingentPaymentsEligibleToReceive" xlink:label="bpmc_CollaborativeArrangementMilestonesContingentPaymentsEligibleToReceive" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_CollaborativeArrangementMilestonesDevelopmentAndRegulatoryMilestonesContingentPaymentsEligibleToReceive" xlink:label="bpmc_CollaborativeArrangementMilestonesDevelopmentAndRegulatoryMilestonesContingentPaymentsEligibleToReceive_637553242402437709" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_CollaborativeArrangementMilestonesContingentPaymentsEligibleToReceive" xlink:to="bpmc_CollaborativeArrangementMilestonesDevelopmentAndRegulatoryMilestonesContingentPaymentsEligibleToReceive_637553242402437709" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_CollaborativeArrangementMilestonesSalesBasedMilestonesContingentPaymentsEligibleToReceive" xlink:label="bpmc_CollaborativeArrangementMilestonesSalesBasedMilestonesContingentPaymentsEligibleToReceive_637553242402437709" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_CollaborativeArrangementMilestonesContingentPaymentsEligibleToReceive" xlink:to="bpmc_CollaborativeArrangementMilestonesSalesBasedMilestonesContingentPaymentsEligibleToReceive_637553242402437709" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsTransactionPriceDetails" xlink:type="extended" xlink:title="41002 - Disclosure - Collaboration and License Agreements - Transaction Price (Details)">
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_CollaborativeArrangementTransactionPrice" xlink:label="bpmc_CollaborativeArrangementTransactionPrice" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_CollaborativeArrangementTransactionPriceUpfrontPayment" xlink:label="bpmc_CollaborativeArrangementTransactionPriceUpfrontPayment_637553242402437709" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_CollaborativeArrangementTransactionPrice" xlink:to="bpmc_CollaborativeArrangementTransactionPriceUpfrontPayment_637553242402437709" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_CollaborativeArrangementTransactionPriceStockIssuedPremiumOnSaleOfStockToCounterparty" xlink:label="bpmc_CollaborativeArrangementTransactionPriceStockIssuedPremiumOnSaleOfStockToCounterparty_637553242402437709" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_CollaborativeArrangementTransactionPrice" xlink:to="bpmc_CollaborativeArrangementTransactionPriceStockIssuedPremiumOnSaleOfStockToCounterparty_637553242402437709" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_CollaborativeArrangementTransactionPriceMilestonePaymentsReceivable" xlink:label="bpmc_CollaborativeArrangementTransactionPriceMilestonePaymentsReceivable_637553242402437709" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_CollaborativeArrangementTransactionPrice" xlink:to="bpmc_CollaborativeArrangementTransactionPriceMilestonePaymentsReceivable_637553242402437709" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_CollaborativeArrangementTransactionPriceInventoryPurchasedByCounterpartyExistingManufacturingInventory" xlink:label="bpmc_CollaborativeArrangementTransactionPriceInventoryPurchasedByCounterpartyExistingManufacturingInventory_637553242402437709" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_CollaborativeArrangementTransactionPrice" xlink:to="bpmc_CollaborativeArrangementTransactionPriceInventoryPurchasedByCounterpartyExistingManufacturingInventory_637553242402437709" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_CollaborativeArrangementTransactionPriceInventoryPurchasedByCounterpartyInProcessManufacturingInventory" xlink:label="bpmc_CollaborativeArrangementTransactionPriceInventoryPurchasedByCounterpartyInProcessManufacturingInventory_637553242402447709" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_CollaborativeArrangementTransactionPrice" xlink:to="bpmc_CollaborativeArrangementTransactionPriceInventoryPurchasedByCounterpartyInProcessManufacturingInventory_637553242402447709" order="5" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationAndLicenseAgreementsSaleOfStockDetails" xlink:type="extended" xlink:title="41003 - Disclosure - Collaboration and License Agreements - Sale of Stock (Details)">
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_StockIssuedDuringPeriodValueNewIssuesPurchaseConsideration" xlink:label="bpmc_StockIssuedDuringPeriodValueNewIssuesPurchaseConsideration" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodValueNewIssues_637553242402447709" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_StockIssuedDuringPeriodValueNewIssuesPurchaseConsideration" xlink:to="us-gaap_StockIssuedDuringPeriodValueNewIssues_637553242402447709" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20210331.xsd#bpmc_StockIssuedDuringPeriodValueNewIssuesPremium" xlink:label="bpmc_StockIssuedDuringPeriodValueNewIssuesPremium_637553242402447709" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_StockIssuedDuringPeriodValueNewIssuesPurchaseConsideration" xlink:to="bpmc_StockIssuedDuringPeriodValueNewIssuesPremium_637553242402447709" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink 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)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount_637553242402447709" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount_637553242402447709" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense_637553242402447709" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense_637553242402447709" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureLeasesComponentsOfLeaseExpenseDetails" xlink:type="extended" xlink:title="41402 - Disclosure - Leases - Components of Lease Expense (Details)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LeaseCost" xlink:label="us-gaap_LeaseCost" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingLeaseCost" xlink:label="us-gaap_OperatingLeaseCost_637553242402457720" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LeaseCost" xlink:to="us-gaap_OperatingLeaseCost_637553242402457720" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SubleaseIncome" xlink:label="us-gaap_SubleaseIncome_637553242402457720" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LeaseCost" xlink:to="us-gaap_SubleaseIncome_637553242402457720" order="2" use="optional" weight="-1" priority="2" />
  </calculationLink>
</linkbase>
