Objective: A difference in survival rates between black and white patients with cancer of the corpus uteri is well established. This study was conducted to determine whether the overexpression of HER2/neu oncogene is associated with poor outcome in uterine serous papillary endometrial cancer, which is a highly aggressive variant of endometrial cancer, and whether a racial difference in the frequency of HER2/neu overexpression may contribute to the disparity in endometrial cancer survival. Study design: Immunohistochemical evaluation was used to examine HER2/neu expression in paraffin blocks from 27 women with stage IA to IV uterine serous papillary endometrial cancer. Univariable analysis was performed and followed by multivariable analysis with Cox’ s proportional hazard model to evaluate whether HER2/neu expression was associated with poor outcome in uterine serous papillary endometrial cancer. Results: Black patients tended to be younger (P =. 02) and have higher HER2/neu expression than white patients (trend P =. 02). Seven of 10 black patients (70% ) showed heavy (3+ ) expression, compared with 4 of 17 white patients (24% ; P =. 04). The association of heavy HER2/neu expression with race persisted after age was controlled through stratification (P =. 05). Earlier deaths from uterine serous papillary endometrial cancer were seen among heavy HER2/neu expressers (P =. 002), black patients (P =. 04), and patients ≤ 65 years old (P =. 04). However, multivariate Cox regression showed that short survival was associated significantly with heavy HER2/neu expression (P =. 02) but not with age (P =. 07) or race (P =. 35), which indicates that HER2/neu expression accounted for much of the race disparity in survival in this patient population. Conclusion: Overexpression of HER2/neu in uterine serous papillary endometrial cancer is an independent variable that is associated with poor outcome, occurs more frequently in black women, and may contribute to racial disparity in survival. HER2/neu expression may guide clinical treatment of patients with uterine serous papillary endometrial cancer and may have implications for the implementation of novel treatment strategies. Objective: A difference in survival rates between black and white patients with cancer of the corpus uteri is well established. Which study was conducted to determine whether the overexpression of HER2 / neu oncogene is associated with poor outcome in uterine serous papillary endometrial cancer, which is a highly aggressive variant of endometrial cancer, and whether a racial difference in the frequency of HER2 / neu overexpression may contribute to the disparity in endometrial cancer survival. Study design: Immunohistochemical evaluation was used to examine HER2 / neu expression in paraffin blocks from 27 women with stage IA to IV uterine serous papillary endometrial cancer. Univariable analysis was performed and followed by multivariable analysis with Cox’s proportional hazard model to evaluate whether HER2 / neu expression was associated with poor outcome in uterine serous papillary endometrial cancer. Results: Black patients tended to be younger (P = .02) and have higher HER2 / neu expression Seven of 10 black patients (70%) showed heavy (3+) expression, compared with 4 of 17 white patients (24%; P =. 04). The association of heavy HER2 / neu expression with race persisted after age was controlled through stratification (P = .05). Earlier deaths from uterine serous papillary endometrial cancer were seen for heavy HER2 / neu expressers (P =. 002), black patients (P = .04) , and patients ≤ 65 years old (P = .04). However, multivariate Cox regression showed that short survival was significantly associated with heavy HER2 / neu expression (P = .02) but not with age (P =. 35), which indicates that HER2 / neu expression accounted for much of the race disparity in survival in this patient population. Conclusion: Overexpression of HER2 / neu in uterine serous papillary endometrial cancer is an independent variable that is associated with poor outcome, occurs more frequently in black women, and may contribute to racial disparity in survival. HER2 / neu expression may guide clinical treatment of patients with uterine serous papillary endometrial cancer and may have implications for the implementation of novel treatment strategies.