Knowledge of reliable prognostic factors is essential in cancer treatment. Especially when intensified treatment is to be considered to improve the overall result, it is desirable to identify well-defined high-risk groups. In a prospective study DNA ploidy and S-phase fraction were measured in 88 patients with endometrial cancer stage I and II. Fresh tumor samples were analyzed using flow cytometry prior to treatment. Diploid tumors represented 84% of the cases, and aneuploid represented 16%. The mean S-phase fraction in diploid tumors was 10%, as compared with 22% in aneuploid tumors. The follow-up time was 5 years in all cases. The survival rate for patients with diploid tumors was 92% and for aneuploid tumors 36%. In the surviving patients, the mean S-phase fraction was 10.4%, a significant difference from 19.9% in the nonsurviving patients (P < 0.001). The highest mortality was found when aneuploidy was combined with an S-phase fraction over 20%, with only 11% survival for 5 years. In diploid tumors with an S-phase fraction below 20%, the survival rate was 92%. In a stepwise regression analysis, S-phase fraction was found to be of the most important prognostic value, followed by myometrial invasion and stage of the tumor and ploidy. Grade was not found to be of any important significance. (C) 1994 Academic Press, Inc.