<?xml version="1.0" encoding="us-ascii"?>
<!--XBRL document created with Merrill Bridge  8.0.1.3 -->
<!--Based on XBRL 2.1-->
<!--Created on: 5/2/2018 4:27:07 PM-->
<!--Modified on: 5/2/2018 4:27:07 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-20180331.xsd#StatementCondensedConsolidatedBalanceSheets" roleURI="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedBalanceSheets" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20180331.xsd#StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss" roleURI="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20180331.xsd#StatementCondensedConsolidatedStatementsOfCashFlows" roleURI="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedStatementsOfCashFlows" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20180331.xsd#StatementCondensedConsolidatedStatementsOfCashFlowsParenthetical" roleURI="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedStatementsOfCashFlowsParenthetical" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20180331.xsd#DisclosureCashEquivalentsAndInvestmentsTabularDisclosureDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCashEquivalentsAndInvestmentsTabularDisclosureDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20180331.xsd#DisclosureFairValueOfFinancialInstrumentsDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureFairValueOfFinancialInstrumentsDetails" />
  <roleRef xlink:type="simple" xlink:href="bpmc-20180331.xsd#DisclosureCollaborationsDetails" roleURI="http://www.blueprintmedicines.com/role/DisclosureCollaborationsDetails" />
  <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/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_Assets" xlink:label="us-gaap_Assets" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_AssetsCurrent" xlink:label="us-gaap_AssetsCurrent_636608752257677185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_AssetsCurrent_636608752257677185" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue_636608752257677185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_636608752257677185" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue_636608752257677185" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_636608752257677185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_636608752257677185" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_636608752257677185" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent" xlink:label="us-gaap_PrepaidExpenseAndOtherAssetsCurrent_636608752257677185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_636608752257677185" xlink:to="us-gaap_PrepaidExpenseAndOtherAssetsCurrent_636608752257677185" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent_636608752257677185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent_636608752257677185" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_636608752257677185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_PropertyPlantAndEquipmentNet_636608752257677185" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_OtherAssetsNoncurrent" xlink:label="us-gaap_OtherAssetsNoncurrent_636608752257677185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_OtherAssetsNoncurrent_636608752257677185" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_RestrictedCashAndCashEquivalentsNoncurrent" xlink:label="us-gaap_RestrictedCashAndCashEquivalentsNoncurrent_636608752257677185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_RestrictedCashAndCashEquivalentsNoncurrent_636608752257677185" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_StockholdersEquity" xlink:label="us-gaap_StockholdersEquity_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_StockholdersEquity_636608752257777185" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_636608752257777185" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit_636608752257777185" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_AdditionalPaidInCapital" xlink:label="us-gaap_AdditionalPaidInCapital_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_636608752257777185" xlink:to="us-gaap_AdditionalPaidInCapital_636608752257777185" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_636608752257777185" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_636608752257777185" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_CommonStockValue" xlink:label="us-gaap_CommonStockValue_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_636608752257777185" xlink:to="us-gaap_CommonStockValue_636608752257777185" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:label="us-gaap_LiabilitiesCurrent_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_LiabilitiesCurrent_636608752257777185" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_AccountsPayableCurrent" xlink:label="us-gaap_AccountsPayableCurrent_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_636608752257777185" xlink:to="us-gaap_AccountsPayableCurrent_636608752257777185" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="us-gaap_AccruedLiabilitiesCurrent_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_636608752257777185" xlink:to="us-gaap_AccruedLiabilitiesCurrent_636608752257777185" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_ContractWithCustomerLiabilityCurrent" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_636608752257777185" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_636608752257777185" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_LeaseIncentivePayableCurrent" xlink:label="us-gaap_LeaseIncentivePayableCurrent_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_636608752257777185" xlink:to="us-gaap_LeaseIncentivePayableCurrent_636608752257777185" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_LoansPayableToBankCurrent" xlink:label="us-gaap_LoansPayableToBankCurrent_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_636608752257777185" xlink:to="us-gaap_LoansPayableToBankCurrent_636608752257777185" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_DeferredRentCreditNoncurrent" xlink:label="us-gaap_DeferredRentCreditNoncurrent_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_DeferredRentCreditNoncurrent_636608752257777185" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent_636608752257777185" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20180331.xsd#bpmc_LeaseIncentivePayableNoncurrent" xlink:label="bpmc_LeaseIncentivePayableNoncurrent_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="bpmc_LeaseIncentivePayableNoncurrent_636608752257777185" order="5" use="optional" weight="1" priority="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_OtherLiabilitiesNoncurrent" xlink:label="us-gaap_OtherLiabilitiesNoncurrent_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_OtherLiabilitiesNoncurrent_636608752257777185" 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/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_NetIncomeLoss_636608752257777185" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_Revenues" xlink:label="us-gaap_Revenues_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss_636608752257777185" xlink:to="us-gaap_Revenues_636608752257777185" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_OperatingExpenses" xlink:label="us-gaap_OperatingExpenses_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss_636608752257777185" xlink:to="us-gaap_OperatingExpenses_636608752257777185" order="2" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_ResearchAndDevelopmentExpense" xlink:label="us-gaap_ResearchAndDevelopmentExpense_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses_636608752257777185" xlink:to="us-gaap_ResearchAndDevelopmentExpense_636608752257777185" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_GeneralAndAdministrativeExpense" xlink:label="us-gaap_GeneralAndAdministrativeExpense_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses_636608752257777185" xlink:to="us-gaap_GeneralAndAdministrativeExpense_636608752257777185" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_NonoperatingIncomeExpense" xlink:label="us-gaap_NonoperatingIncomeExpense_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss_636608752257777185" xlink:to="us-gaap_NonoperatingIncomeExpense_636608752257777185" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="us-gaap_OtherNonoperatingIncomeExpense_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NonoperatingIncomeExpense_636608752257777185" xlink:to="us-gaap_OtherNonoperatingIncomeExpense_636608752257777185" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_InterestAndDebtExpense" xlink:label="us-gaap_InterestAndDebtExpense_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NonoperatingIncomeExpense_636608752257777185" xlink:to="us-gaap_InterestAndDebtExpense_636608752257777185" order="2" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:label="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_636608752257777185" order="2" use="optional" weight="1" priority="3" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedStatementsOfCashFlows" xlink:type="extended" xlink:title="00300 - Statement - Condensed Consolidated Statements of Cash Flows">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities_636608752257777185" order="1" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_ProfitLoss" xlink:label="us-gaap_ProfitLoss_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636608752257777185" xlink:to="us-gaap_ProfitLoss_636608752257777185" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_DepreciationDepletionAndAmortization" xlink:label="us-gaap_DepreciationDepletionAndAmortization_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636608752257777185" xlink:to="us-gaap_DepreciationDepletionAndAmortization_636608752257777185" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_AmortizationOfFinancingCosts" xlink:label="us-gaap_AmortizationOfFinancingCosts_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636608752257777185" xlink:to="us-gaap_AmortizationOfFinancingCosts_636608752257777185" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20180331.xsd#bpmc_AccretionOfPremiumsAndDiscountsOnInvestments" xlink:label="bpmc_AccretionOfPremiumsAndDiscountsOnInvestments_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636608752257777185" xlink:to="bpmc_AccretionOfPremiumsAndDiscountsOnInvestments_636608752257777185" order="4" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayable" xlink:label="us-gaap_IncreaseDecreaseInAccountsPayable_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636608752257777185" xlink:to="us-gaap_IncreaseDecreaseInAccountsPayable_636608752257777185" order="5" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20180331.xsd#bpmc_IncreaseDecreaseInCustomerAssets" xlink:label="bpmc_IncreaseDecreaseInCustomerAssets_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636608752257777185" xlink:to="bpmc_IncreaseDecreaseInCustomerAssets_636608752257777185" order="6" use="optional" weight="-1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets" xlink:label="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636608752257777185" xlink:to="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_636608752257777185" order="7" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_ShareBasedCompensation" xlink:label="us-gaap_ShareBasedCompensation_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636608752257777185" xlink:to="us-gaap_ShareBasedCompensation_636608752257777185" order="8" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_IncreaseDecreaseInOtherNoncurrentAssets" xlink:label="us-gaap_IncreaseDecreaseInOtherNoncurrentAssets_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636608752257777185" xlink:to="us-gaap_IncreaseDecreaseInOtherNoncurrentAssets_636608752257777185" order="9" use="optional" weight="-1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_IncreaseDecreaseInAccruedLiabilities" xlink:label="us-gaap_IncreaseDecreaseInAccruedLiabilities_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636608752257777185" xlink:to="us-gaap_IncreaseDecreaseInAccruedLiabilities_636608752257777185" order="10" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20180331.xsd#bpmc_IncreaseDecreaseInContractWithCustomerLiability" xlink:label="bpmc_IncreaseDecreaseInContractWithCustomerLiability_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636608752257777185" xlink:to="bpmc_IncreaseDecreaseInContractWithCustomerLiability_636608752257777185" order="11" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20180331.xsd#bpmc_IncreaseDecreaseInDeferredRent" xlink:label="bpmc_IncreaseDecreaseInDeferredRent_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636608752257777185" xlink:to="bpmc_IncreaseDecreaseInDeferredRent_636608752257777185" order="12" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities_636608752257777185" order="2" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_RepaymentsOfBankDebt" xlink:label="us-gaap_RepaymentsOfBankDebt_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_636608752257777185" xlink:to="us-gaap_RepaymentsOfBankDebt_636608752257777185" order="1" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_PaymentsOfStockIssuanceCosts" xlink:label="us-gaap_PaymentsOfStockIssuanceCosts_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_636608752257777185" xlink:to="us-gaap_PaymentsOfStockIssuanceCosts_636608752257777185" order="2" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:label="us-gaap_ProceedsFromIssuanceOfCommonStock_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_636608752257777185" xlink:to="us-gaap_ProceedsFromIssuanceOfCommonStock_636608752257777185" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities_636608752257777185" order="3" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_636608752257777185" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_636608752257777185" order="1" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:label="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_636608752257777185" xlink:to="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_636608752257777185" order="2" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities" xlink:label="us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_636608752257777185" xlink:to="us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities_636608752257777185" order="3" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/StatementCondensedConsolidatedStatementsOfCashFlowsParenthetical" xlink:type="extended" xlink:title="00305 - Statement - Condensed Consolidated Statements of Cash Flows (Parenthetical)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_636606940434827358" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_636606940434827358" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue_636608752257777185" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_RestrictedCashAndCashEquivalents" xlink:label="us-gaap_RestrictedCashAndCashEquivalents_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_636606940434827358" xlink:to="us-gaap_RestrictedCashAndCashEquivalents_636608752257777185" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCashEquivalentsAndInvestmentsTabularDisclosureDetails" xlink:type="extended" xlink:title="40301 - Disclosure - Cash Equivalents and Investments - Tabular Disclosure (Details)">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_636608752257777185" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities_636608752257777185" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_CashEquivalentsAtCarryingValue" xlink:label="us-gaap_CashEquivalentsAtCarryingValue" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure" xlink:label="us-gaap_CashAndCashEquivalentsFairValueDisclosure_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashEquivalentsAtCarryingValue" xlink:to="us-gaap_CashAndCashEquivalentsFairValueDisclosure_636608752257777185" order="1" 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/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_AssetsFairValueDisclosure" xlink:label="us-gaap_AssetsFairValueDisclosure" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsFairValueDisclosure" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities_636608752257777185" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2017/elts/us-gaap-2017-01-31.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure" xlink:label="us-gaap_CashAndCashEquivalentsFairValueDisclosure_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsFairValueDisclosure" xlink:to="us-gaap_CashAndCashEquivalentsFairValueDisclosure_636608752257777185" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.blueprintmedicines.com/role/DisclosureCollaborationsDetails" xlink:type="extended" xlink:title="40601 - Disclosure - Collaborations (Details)">
    <loc xlink:type="locator" xlink:href="bpmc-20180331.xsd#bpmc_NonrefundableUpfrontAndMilestonePaymentReceived" xlink:label="bpmc_NonrefundableUpfrontAndMilestonePaymentReceived" />
    <loc xlink:type="locator" xlink:href="bpmc-20180331.xsd#bpmc_NonrefundableUpfrontPaymentReceived" xlink:label="bpmc_NonrefundableUpfrontPaymentReceived_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_NonrefundableUpfrontAndMilestonePaymentReceived" xlink:to="bpmc_NonrefundableUpfrontPaymentReceived_636608752257777185" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="bpmc-20180331.xsd#bpmc_NonrefundableMilestonePaymentReceived" xlink:label="bpmc_NonrefundableMilestonePaymentReceived_636608752257777185" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="bpmc_NonrefundableUpfrontAndMilestonePaymentReceived" xlink:to="bpmc_NonrefundableMilestonePaymentReceived_636608752257777185" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
</linkbase>
