A 68-year-old women with polycythemia vera was treated with hydroxyurea for 8 years and developed painful ulcers on her lower legs, multiple hypertrophic actinic keratoses and a squamous cell carcinoma. After discontinuing hydroxyurea therapy the leg ulcers resolved within 8 weeks. The hypertrophic actinic keratoses and squamous cell carcinoma were treated with cryotherapy and excision, respectively. Hydroxyurea induces a variety of cutaneous side effects such as painful leg ulcers and squamous cell carcinomas. Given the wide variety of adverse cutaneous side effects associated with long-term hydroxyurea therapy, the first step in management is to insure that physicians and patients are aware of the specific risks of this treatment. Patients under hydroxyurea therapy should be monitored closely by dermatologists to early detect and treat the cutaneous side effects.