We report a case of a 76-year-old woman with concurrent onset of two primary cutaneous malignancies, one at the fourth finger and another at the dorsum of the same hand. The patient was on long-term therapy with hydroxyurea (HU) for polycythemia vera. Histopathologic and immunohistochemical studies revealed two different malignant cutaneous lesions, i.e. basal cell carcinoma (positive for bcl-2 and negative for vimentin, EMA and CK5/6) and poorly differentiated sarcomatoid squamous cell carcinoma (positive for vimentin, EMA and cytokeratins CK5/6, and negative for bcl-2). In addition, p53 was positive in approximately 50% of squamous cell carcinoma cells and in almost all basal cell carcinoma cells. The presence of low-risk human papillomavirus (HPV, types 6, 11) was verified by polymerase chain reaction, but only in the surrounding normal skin tissue, whereas HPV infection could not be detected in either carcinoma. In this patient, concurrence of two different skin carcinomas on sun-exposed skin, in the absence of HPV, suggest direct involvement of potentially mutagenic HU therapy, through influence on DNA synthesis and repair mechanisms, in conjunction with ultraviolet exposure. Therefore, we suggest that in patients on HU therapy with cutaneous side effects, referral to a dermatologist should be obligatory.