5 patients developed acute nonlymphocytic leukemia (ANLL) 2–4 years following the use of various cytotoxic agents for other primary disease. Alkylating agents were responsible for development of ANLL in 3 patients while mitomycin-C and methotrexate appear to be linked with leukemia transformation in the remaining 2 patients. 3 patients had a prolonged preleukemic phase preceding ANLL. Pancytopenia observed in 4 of 5 patients favors drug-induced stem cell damage leading to relatively resistant leukemia. Although the incidence of secondary leukemia is not very high, careful use of cytotoxic agents is needed to minimize therapy-linked neoplasms.