Leukemia cutis was documented by biopsy in 18 of 877 patients (2%) with acute myelogenous leukemia (AML) seen at Roswell Park Memorial Institute (Buffalo, NY) between 1969 and 1986. French-American-British (FAB) types included four M2, one M3, ten M4, and three M5. Lysozyme was more consistently detectable in skin sections in our cases than Leu-M1, alpha-1-antitrypsin, alpha-1-antichymotrypsin, or chloroacetate esterase activity. Additional extramedullary sites of involvement were present in 16 patients, including meningeal leukemia in six. Two patients had leukemia cutis preceding bone marrow leukemia. Skin was the initial site of relapse in 11 patients, without marrow relapse, occurring as late as 5.5 years after diagnosis. Most patients in this retrospective series were treated with radiation therapy and/or palliative chemotherapy, and did poorly, with prompt bone marrow relapses and serial skin relapses. Long-term disease-free survival was achieved in the one patient whose skin relapse was treated with whole-body electron-beam radiation therapy in conjunction with reinduction and consolidation chemotherapy. Severe skin toxicity was caused by administration of Adriamycin (doxorubicin) 12 days after electron-beam irradiation in one patient, but was not seen when cytosine arabinoside was administered in doses up to 3 g/m2 in conjunction with radiation therapy. This retrospective review suggests that optimal management of AML involving skin might include whole-body electron-beam irradiation in conjunction with induction or reinduction chemotherapy without anthracyclines, followed by consolidation chemotherapy. Additionally, there should be ongoing surveillance for and treatment of extramedullary disease at other sites, including the meninges.