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The presence of KMT2A/AFF1 rearrangement in B‐lymphoblastic leukemia (B‐ALL) is an independent poor prognostic factor and has been associated with higher rate of treatment failure and higher risk of linage switch under therapy. Blinatumomab has shown promising therapeutic results in refractory or relapsed B‐ALL; however, it has potential risk of inducing lineage switch, especially in KMT2A/AFF1 rearranged B‐ALL into acute myeloid leukemia and/or myeloid sarcoma. We report a 40‐year‐old female with KMT2A/AFF1‐rearranged B‐ALL that was refractory to conventional chemotherapy. Following administration of blinatumomab, she developed a breast mass proven to be myeloid sarcoma, in addition to bone marrow involvement by AML. Approximately six weeks after cessation of blinatumomab, a repeat bone marrow examination revealed B/myeloid MPAL.