We describe 2 patients with systemic sclerosis (scleroderma) who developed severe localized skin thickening following radiation therapy for cancer. Radiation therapy may result in intense localized areas of fibrosis in patients with scleroderma. The fibrosis may extend beyond the irradiation portals and result in damage to underlying viscera. Radiotherapy may precipitate scleroderma or cause a generalized worsening of the underlying disease.