Hydroxyurea (HU) has been shown to induce a variety of cutaneous adverse reactions, including severe leg ulcers. This report shows a successful treatment of a HU-induced chronic wound associated with squamous cell carcinomas (SCC). A 62-year-old patient affected with polycythemia vera and treated with HU for 10 years, presented with a non healing ulcer on a left heel. The patient gave a history of suffering from the wound for over 2 years. Biopsy showed evidence of invasive SCC. The patient underwent Mohs surgery and a greater saphenous vein ablation for polycythemia vera-associated vascular complications. The wound consistently decreased in size following successive debridements and coverage with human skin equivalent. The wound healed completely after a 6-month period. A multidisciplinary team approach to the treatment proved to be effective resulting in healing of this multifactorial chronic ulcer.