Trisomy 4 is a newly recognized primary chromosome change in leukemia. Five cases of acute nonlymphocytic leukemia (ANLL) are described from the United States and France. As in cases from Belgium, the only chromosome abnormality detected in the leukemic cells was trisomy 4. This was associated preferentially with ANLL of the M4 type (by FAB classification): acute myelomonocytic leukemia.