The association of ankle ulcer development with hydroxyurea therapy in patients with myeloproliferative disorders has been reported in two small case series and two patient reports. It is thought that hydroxyurea, an antineoplastic agent with selective cytotoxicity for cells that divide most actively (such as those of the skin), causes these ulcerations through impairment of normal wound healing in areas of common trauma. Treatment modalities reported include discontinuation of medication, debridement, and topical antibiotics. We report the successful split-thickness skin grafting of a hydroxyurea-related ankle ulceration after preoperative discontinuation of hydroxyurea treatment in a patient with chronic myelogenous leukemia who had previously failed grafting while taking this medication. It is hoped that heightened awareness of the link between hydroxyurea and chronic, debilitating ankle ulcerations in patients with myeloproliferative disorders, as well as familiarity with reported treatments, will promote early diagnosis and aggressive management of these unique and relatively uncommon lesions.