A 32-year-old man was diagnosed with acute lymphoblastic leukemia (panel A; original magnification ×100, Wright-Giemsa stain). Initial cytogenetics showed 46,XY,t(5;14)(q31;q32). He achieved remission with induction and then underwent allogeneic hematopoietic cell transplantation (HCT) from his HLA-matched sister (46 years old). He had an uneventful posttransplant course. One-month posttransplant, bone marrow (BM) karyotype showed 46,XX[20] (panel B). Routine 1-year BM biopsy revealed mildly hypercellular marrow with myeloid hyperplasia and monocytosis. Cytogenetics showed new donor-derived clonal evolution with 46,XX,t(3;13)(p10;q10), inv(11)(p15q23)[18]/46,XX[2] (panel C). His complete blood count was within normal limits and, therefore, the decision was made to follow without treatment. His donor sister was examined, and BM biopsy showed normal hematopoiesis, with normal female karyotype. Repeated patient BM biopsy 3 months later showed transformation to acute monocytic leukemia, with 21% blasts and blast equivalents (panel D; original magnification ×100, Wright-Giemsa stain) and persistent abnormal female karyotype. The patient achieved complete cytogenetic remission (46,XX[20]) with induction and then underwent a second allogeneic HCT from his other matched sister (55 years old).Donor-derived clonal myeloid neoplasm is a rare complication encountered after allogeneic HCT. Investigating the origin of relapsed leukemia cells post allogeneic HCT is critical in directing therapy afterward, especially if a second allogeneic HCT is a possible therapeutic option.