OBJECTIVE We previously described vascular invasion-associated changes, defined as the presence of vascular invasion or perivascular lymphocytic infiltrates, as key prognostic indicators in stage I endometrioid carcinoma. The current study was undertaken to examine the prognostic value of HER-2/neu expression in relation to other factors, including vascular invasion-associated changes, in surgical stage I endometrioid carcinoma. STUDY DESIGN Seventy-one patients with surgical stage I endometrioid carcinoma treated by hysterectomy and followed up were randomly chosen for retrospective analysis of prognostic indicators including standard clincopathologic features, deoxyribonucleic acid ploidy, and HER-2/neu expression. The latter was examined by an objective computerized quantitative immunohistochemical system. RESULTS By univariate analysis many factors were found to correlate with outcome, including age, tumor grade, depth of invasion, ploidy, HER-2/neu expression, and vascular invasion-associated changes. By multivariate analysis only vascular invasion-associated changes, aneuploidy, and HER-2/neu overexpression were found to independently correlate with survival. Stratification of patients on the basis of these three features revealed survival rates of 100%, 92%, and 60% when none, one, and two or three features were present, respectively. CONCLUSION This study suggests that HER-2/neu expression correlated with outcome independent of other factors in endometrial carcinoma and may aid in estimating prognosis. The prognostic value of HER-2/neu overexpression independent of vascular invasion suggests that this factor may operate by increasing the ability of tumor cells to grow at a distal site once vascular invasion occurs.