The association of multiple cutaneous cancers and long-term use of hydroxyurea is now being recognized. In this article, we describe the development of multiple skin tumors in two patients who were receiving hydroxyurea therapy. These cases illustrate the late onset of subsequent skin cancers despite discontinuation of therapy. As hydroxyurea continues to have a prominent role in the treatment of myeloproliferative diseases, clinicians must be aware of the increased risk of multiple skin cancers and use preventive and skin cancer screening practices in patients with these diseases.