In a prospective study, the prognostic significance of clinical and flow cytometric variables was evaluated in univariate and multivariate analyses of 489 cases of endometrial adenocarcinoma. Age, uterine cavity depth, stage, histopathologic grade, myometrial invasion, ploidy level, and S-phase fraction were of prognostic value in the univariate analysis. In a multivariate analysis of clinical variables, age and uterine cavity depth were insignificant. When adding flow cytometric variables (DNA content and S-phase fraction) separately to the clinical variables, the significance of myometrial invasion was reduced, and histopathologic grade became nonsignificant when S-phase fraction was included. When adding both DNA content and S-phase fraction, the DNA content became prognostically insignificant. S-phase fraction was, next to clinical stages III and IV, found to be the strongest predictor of outcome. It is concluded that S-phase fraction is a new, objective parameter that can be used for the identification of prognostically different subgroups of patients within a given stage and grade.