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OBJECTIVE: To describe the incidence of cancer in a large cohort of patients with systemic sclerosis (SSc) and compare it to the Surveillance Epidemiology and End Results (SEER) cancer registries. METHODS: Cancer risk in a large cohort of patients with SSc followed at our institution was assessed. A total of 769 patients with SSc who were followed between 1987 and 2002 were screened for the development of cancer. Standardized incidence ratios (SIR) for malignancies identified after diagnosis of SSc were calculated using the SEER cancer registries and stratified by sex. RESULTS: Ninety malignancies were diagnosed in 769 patients followed at our institution between 1987 and 2002. Sixty-two malignancies were diagnosed after diagnosis of SSc in a total of 3,775 patient years of followup. Twenty-eight malignancies were diagnosed prior to diagnosis of SSc. The SIR for all cancers diagnosed after diagnosis of SSc was 1.55 (1.16-1.93). The SIR for esophageal cancer was 15.9 (4.2-27.6) while that of oropharyngeal cancer was 9.63 (2.97-16.29). CONCLUSION: We identified an overall increase in the incidence of cancer in a cohort of patients with SSc compared to the general population, with statistically significant differences in the incidence of esophageal and oropharyngeal cancers.