A 23-month-old female evaluated for profound anemia proved to have megakaryoblastic leukemia. The diagnosis is based on examination of bone marrow morphology, cytochemical characteristics, and immunophenotype. The chromosome complement of unstimulated blast cells in peripheral blood and bone marrow was 48,XX,+21,+21. Tetrasomy 21 is the sole clonal cytogenetic abnormality in this patient with megakaryoblastic leukemia. The constitutional complement of the patient is normal female, 46,XX.