We treated 15 patients with therapy related acute nonlymphocytic leukemia (tANLL) or therapy related myelodysplastic syndrome (tMDS) who had no rearrangements of chromosomes 5 and/or 7 or complex cytogenetic rearrangements by intensive chemotherapy. The median age was 43 years. Seven patients had one of the "specific" rearrangements of de novo ANLL (inv(16), t(8;21), t(15;17)or t(9;11)). Eight patients had a normal karyotype (4 cases) or single cytogenetic rearrangements not involving chromosomes 5 and 7: trisomy 8 (2 cases), t(1,2)(1 case), 20q deletion (1 case). All 7 patients with "specific" rearrangements had tANLL at presentation, without a preceding myelodysplastic phase. Seven of the 8 patients with a normal karyotype or other single cytogenetic rearrangements presented with tMDS, and the remaining patient with tANLL. Twelve patients achieved complete remission (CR), 2 had hypoplastic death and 1 had resistant disease. Median actuarial disease free interval (DFI) was 30 months. No significant prognostic factor for achieving CR was found. Significantly longer DFI was found in patients with "specific" chromosome rearrangements, compared to other karyotypes, and in patients who presented with tANLL, compared to those who presented with tMDS. Those 2 prognostic factors strongly correlated. In contrast to tANLL and tMDS with rearrangements of chromosomes 5 and/or 7 or complex karyotypes, patients with tANLL or tMDS who had other abnormal cytogenetic findings seem to achieved a high CR rate with intensive chemotherapy. tANLL with "specific" rearrangements achieved prolonged CR in many cases, whereas tMDS with other abnormal karyotypes generally had short CR, like their de novo counterparts.