Malignant pyoderma of the right ear developed in a 58-year-old woman, and it spread insidiously over the entire right side of the face. Pyoderma gangrenosum was diagnosed on the basis of clinical and histologic findings and the patient's history of ulcerative colitis and sclerosing cholangitis. After successive therapeutic failures with a score of conventional approaches over an 18-month period, oral cyclosporine, 10 mg/kg/day, was started. Significant healing of the skin was noted within 1 month. There was an associated remission of the patient's cholangitis and inflammatory bowel disease. The dosage of cyclosporine was progressively tapered and then discontinued after 7 months, when healing was complete. No relapse occurred in the subsequent 14 months, and there was an associated remission of the patient's cholangitis and inflammatory bowel disease. Cyclosporine merits serious attention for treatment of both pyoderma gangrenosum and sclerosing cholangitis.