A 52-year-old man developed therapy-related acute myeloid leukemia (AML) following prolonged immunosuppression with azathioprine for polymyositis. Karyotypic analysis showed deletions of the short arm of chromosome 7 and the long arm of chromosome 5. The importance of recognizing this potential complication while treating benign rheumatological and immunological diseases with purine analogues like azathioprine is emphasized. Therapy-related AML is a poor prognostic group that does not respond favourably to standard induction therapy.