The use of pegylated interferon (PEG-IFN) and ribavirin is considered standard therapy for patients with chronic hepatitis C. Many adverse effects of IFN appear to be of autoimmune origin. Vitiligo is a hypomelanotic disease, whose cause, despite many investigations, remains unknown, although some evidence points to an autoimmune pathogenesis. This report describes a case of vitiligo that occurred during the third month of treatment with PEG-IFN and ribavirin. The sustained virologic response was the result of a 52-week regimen; however, hypomelanotic cutaneous patches persisted. Autoimmune adverse effects of IFN therapy, which may include vitiligo, should be carefully monitored. The decision about whether to discontinue treatment should be discussed with the patient, who must be informed that the lesions may persist.