The association between systemic sclerosis and malignancy was evaluated in the Pittsburgh standard metropolitan statistical area during 1971-1982 and compared with data for this geographic area from the Third National Cancer Survey of 1969-1971. Fourteen malignancies were detected in 262 systemic sclerosis patients (5%) during a followup period that included 1,335 patient-years. After adjustment for age and sex, the expected number of malignancies was 7.72 (relative difference = 1.81; P = 0.05). This increased relative difference was predominantly due to an increase in observed lung cancer (relative difference = 4.4; P less than 0.05), which occurred in the setting of long-standing pulmonary fibrosis but was not associated with cigarette smoking. Although breast cancer was no more frequent than expected, it tended to occur in close temporal relationship with the onset of systemic sclerosis. These findings suggest a biologic relationship between systemic sclerosis and certain malignant neoplasms.