Therapy-related acute nonlymphocytic leukemias occur with increasing frequency owing to modern aggressive antineoplastic therapies. Out of 3,138 bone marrow trephine biopsies, there were 148 cases of acute nonlymphocytic leukemias. Of these, 14 cases occurred 30-156 months following chemotherapy or radiotherapy or both for malignant disease. The male/female ratio was 0.27 (vs. 1.6 of "de novo" leukemias). Primary malignancies (7 Hodgkin's disease, 1 fibrosarcoma and 6 carcinomas) had been treated with chemotherapy+radiotherapy (10 cases), with chemotherapy alone (3 cases) or with radiotherapy alone (1 case) and were apparently cured. All therapy-related leukemias were heralded by a preleukemic cytopenic phase. Response to therapy was poor (mean survival 3.9 months). Bone marrow histopathological findings showed in 13 cases acute myelo- or monoblastic leukemia and in 1 case erythroleukemia. Out of 21 biopsies, there were increased numbers of abnormal megakaryocytes in 10, megaloblastic dyserythropoiesis in 7, and fibrosis in 13 (moderate in 11 cases and severe in 2, with dry tap). Therapy-related acute leukemia appears to be a distinct clinical-pathological entity. Bone marrow trephine biopsy is useful because of the frequency of fibrosis, the possibility of dry tap, and the characteristic histopathological findings that make diagnosis possible also in the preleukemic phase.