The effective treatment of childhood malignancies has increased the importance of early detection and treatment of second malignant neoplasms. Anticancer drugs may also be leukemogenic agents, by the same mechanisms that kill cancer cells. We report the case of a 10-year-old boy who had received radiotherapy and chemotherapy for the treatment of Ewing's sarcoma and developed acute lymphoblastic leukemia 22 months after the diagnosis of primary malignancy. Although chemotherapy is well known to potentiate the development of second acute nonlymphocytic leukemia, the pathogenic factors leading to second acute lymphoblastic leukemia remain obscure.