A 75-year-old male was diagnosed with carcinoma in-situ of the bladder. He failed standard therapy and was started on pembrolizumab to prevent the need for cystectomy. His malignancy recurred, and he was treated with intravesical valrubicin and gemcitabine/docetaxel. Three years after starting pembrolizumab, he developed severe neutropenia and thrombocytopenia. He was treated for suspected auto-immune cytopenias but was later found to have acute promyelocytic leukemia on peripheral blood smear and cytometry. He was hospitalized, treated with all-trans retinoic acid and arsenic trioxide, and is currently in molecular remission.This case describes therapy-related acute promyelocytic leukemia (t-APL) diagnosed while on pembrolizumab. Pembrolizumab is an immune checkpoint inhibitor that exhibits anti-tumor effects. Development of hematologic malignancies after immune checkpoint inhibitor therapy is rare. The definitive etiology of our patient's t-APL is uncertain; however, it is more likely that he developed de novo acute promyelocytic leukemia (APL), which was suppressed by pembrolizumab and later revealed when pembrolizumab was discontinued.