INTRODUCTION: Endometrial cancer (EC) is the most common gynecologic cancer in the United States. Racial disparities in the incidence and mortality of this cancer are apparent; black women are less likely to develop this malignancy, and yet are more likely to die when diagnosed. Racial differences of second primary cancer (SPC) have not been examined and are the goal of this study. METHODS: Using the National Cancer Institute's Surveillance, Epidemiology, and End Results database, SPC risk in white and black EC cases was compared to the general population and to women with other primary cancers. Standardized incidence ratios (SIRs) of SPC (overall and by tumor site) with 95% confidence intervals were calculated. Poisson regression was used to estimate the race-specific risk of SPC in EC cases treated with radiotherapy vs. non-irradiated cases. RESULTS: The analysis included 11,047 EC cases diagnosed between 1973 and 2007 that developed a SPC. Overall risk of SPC in white EC cases was significantly lower than the general population (SIR=0.85, 95% CI: 0.84, 0.87), but significantly higher in black EC cases (SIR=1.19, 95% CI: 1.08, 1.31). White EC cases treated with radiotherapy were more likely to develop SPC compared to non-irradiated cases (IRR=1.18, 95% CI: 1.14, 1.23). CONCLUSIONS: This is the first analysis of race-specific SPC risk in EC cases and it suggests differences between white and black cases. Although exploratory, these data provide important clues about the etiology of SPC in patients with EC. This analysis also highlights the need for careful monitoring following diagnosis and treatment of EC.