Relapse after 5 years of complete remission (CR) is uncommon in acute myeloid leukemia (AML). Among 2347 patients seen between 1980 and 2008, 1366 achieved CR; 942 relapsed. Eleven (1.16% of all relapses) relapsed after a CR of >5 years. The median age was 66 years (range, 37-79). Initial therapy was cytarabine plus anthracycline in six, amsacrine-based in three, and other in two. The median CR1 duration was 81 months (range, 60-137). At relapse, the karyotype was different from the initial finding in five of eight (63%) patients with available data. Treatment for relapse included cytarabine with anthracycline in eight, and other in three patients, with a second CR (CR2) achieved in four (36%). The median CR2 duration was 1 month (range, 0-37), and median survival after relapse was 6.4 months (range, 1-39). Late relapses in AML are infrequent, with poor response to therapy. Karyotype at relapse is frequently different, raising the question of second AML versus relapse with the original clone.