Squamous cell carcinoma (SCC) is a rare complication of cutaneous lupus erythematosus (LE). Aside from the documented role of ultraviolet light, SCC may arise in areas of chronic scarring, such as in lesions of discoid LE. Iatrogenic immunosuppression associated with organ transplantation also results in a predisposition to SCC, often with multiple tumors. A role for certain human papillomaviruses (HPV) in the development of squamous cell carcinoma has been documented; specifically, HPV types 5 and 8 are detected in SCCs in patients with epidermodysplasia verruciformis and in recipients of organ transplants. HPV-11 is generally found in benign genital condylomata or laryngeal papillomas, but has not yet been associated with malignancy. We describe a patient with non-scarring cutaneous LE who was treated with azathioprine and prednisone and developed multiple SCCs. HPV-11 DNA and the target oncogenes neu and Ki-ras were detected in tumor tissue with the polymerase chain reaction. The HPV may have been involved in tumor induction and the azathioprine may have been involved in tumor promotion.