Twenty-three patients with de novo acute myeloid leukemia (AML) and t(8;21) (q22;q22), including 2 children aged 7 and 14 and 21 adults aged 16 to 68 (median 29), were treated with intensive chemotherapy and 22 (96%) achieved complete remission (CR). Three were allografted in first CR. Median actuarial disease-free interval (DFI) was 17 months in the 22 patients and 14 months when the 3 allografted patients (who did not relapse) were excluded, as compared to 19.5 months in our whole series of AML treated according to the same protocol. After relapse, most patients with t(8;21) reached a second CR, but it was short, except in the 4 patients who were then allografted, and for whom follow-up is insufficient to draw any conclusion. Our findings suggest that, although it is associated with a high CR rate, AML with t(8;21) has a high incidence of relapses, especially in the first year of CR. The term "favorable" cytogenetic rearrangement may be misleading in such cases, and we believe that these patients should receive intensive post-consolidation therapy, possibly including an allograft whenever feasible.