Therapy-related acute myeloid leukemia (t-AML) in most cases develops after chemotherapy of other malignancies and shows characteristic chromosome aberrations. Two general types of t-AML have previously been identified. One type is observed after therapy with alkylating agents and characteristically presents as therapy-related myelodysplasia with deletions or loss of the long arms of chromosomes 5 and 7 or loss of the whole chromosomes. The other type is observed after therapy with topoisomerase II inhibitors and characteristically presents as overt t-AML with recurrent balanced chromosome aberrations. Recent research suggests that these 2 general types of t-AML can now be subdivided into at least 8 genetic pathways with a different etiology and different biologic characteristics.