Abstract We report a rare case of a 17-year-old female with overlap syndrome (systemic lupus erythematosus and systemic sclerosis) who developed severe abdominal pain and bloody diarrhea accompanied by central nervous system lupus. Colonoscopy revealed multiple irregular and linear ulcers throughout the colon, which were resistant to corticosteroid pulse therapy and plasma exchange. The patient finally recovered after treatment with a relatively low dose of monthly intravenous cyclophosphamide (250 mg/m(2)) pulse therapy.