Background Endometrial tumor represents the sixth most common tumor in women all over the world. HER2/neu protein overexpression was related to tumor cell proliferation and survival pathways in some malignancies. Uterine carcinomas are comparatively rare tumors that overexpress HER2/neu. Studies of the percentages of endometrial adenocarcinomas that overexpress HER2/neu have ranged from 13 to 50% with almost half of that fraction accompanied by gene amplifications. Patients and methods This is a retrospective case series study involving 38 cases diagnosed as endometrial carcinoma from January 2014 to December 2018 with full medical records in Ain Shams University Oncology Hospital and in the Early Cancer Detection Unit at Ain Shams University Hospitals. The study includes pathologically proven high-grade endometrial cancers. Immunohistochemical expression for HER2/neu was scored and analyzed. Results HER2/neu expression was positive in 36.8% of patients. HER2/neu score was negative in 57.9%, score 1 in 5.3%, score 2 in 18.4%, and score 3 in 18.4% of cases. A statistically significant association was found among HER2/neu expression and lymphovascular invasion (P<0.05), lymph node metastasis (P<0.05), distant metastasis (P<0.02), and a highly significant association with FIGO surgical tumor stage (P<0.003). Conclusions Although our results did not reach a significant association among HER2/neu-expressions and total survival, further studies on a larger sample size are recommended to validate its value as a potential predictive marker noted from the positive correlation between its expression and other prognostic factors including lymphovascular invasion, lymph node metastasis, distant metastasis, and FIGO surgical tumor stage.