Among 50 cases of acute nonlymphocytic leukemia (ANLL) with available cytogenetic data seen in our section since May 1988, two were found to carry a monosomy 21 abnormality which has been rarely reported in hematologic malignancies. The first case is a 58-year-old male with a diagnosis of AML, FAB M2, who died of refractory leukemia 9 months later. The other case is a 59-year-old female with AML, FAB M2. Complete remission was achieved initially but she died of sepsis 3 months later with no evidence of leukemic relapse. Monosomy 21 is not yet recognized as a nonrandom cytogenetic abnormality in ANLL, whereas its unusual predilection in AML, especially the FAB M2 or M4 categories, as noted in our study and others' reports, have raised this possibility. Further studies and the accumulation of new cases are needed in the hope of defining it as a subtype of ANLL.