Purpose: Leukemia cutis (LC) is the infiltration of the epidermis, dermis, or subcutis by neoplastic leukocytes, resulting in clinically identifiable cutaneous lesions. Electron-based radiation therapy (RT) is often used in the treatment of LC; however, modern studies of RT are lacking. We reviewed our experience to analyze treatment response, disease control, and toxicity associated with RT in order to develop treatment recommendations for patients with LC. Methods and Materials: Fifteen patients who underwent treatment for LC at our institution from November 1994 to August 2009 were identified and their medical records were reviewed and analyzed. Results: LC presented after a median of 2 (range 0-24) months from acute myeloid leukemia diagnosis. Median survival from time of LC presentation was 23 months (range 0.5-137 months). Thirteen courses of radiation were administered to 12 patients: 9 total skin electron beam (TSEB) therapy and 4 focal treatments. Of patients receiving TSEB, 89% had diffuse LC involvement and 67% were in marrow remission. By contrast, only 25% of patients receiving focal therapy had diffuse LC involvement and only 25% were in marrow remission. Median TSEB dose was 1600 (range 600-2400) cGy. Fifty percent of patients had a complete response to RT but 1-year local control was only 33%. All patients who developed a skin relapse either had active marrow disease at the time of RT or marrow recurrence shortly thereafter. Median survival since RT was 5 (range 0.5-136) months. RT was well tolerated without significant acute effects; however, 1 patient receiving chemotherapy developed radiation recall 1 month after RT. Conclusions: Patients with LC have aggressive disease with few long-term survivors. Definitive treatment with TSEB should be utilized only in cases of marrow remission with focal electron therapy reserved for palliation of symptomatic lesions. Long-term prognosis and durable cutaneous remission is dependent on systemic disease control.