Two patients with M2 subtype of acute nonlymphocytic leukemia (ANLL) and trisomy 4 as a primary karyotype change are described. The abnormality was observed in 100% of bone marrow (BM) metaphases in both cases. It appeared alone in one case and was associated with trisomy 13 in 94% of metaphases in the other, These are the second and third cases of ANLL with trisomy 4 documented in Italy. Neither patient appears to have incurred any environmental or therapeutic insult.