In a histopathological review of 266 women with stage I-IV endometrial carcinoma, the prognostic significance of uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CCC) of the endometrium was compared with that of ordinary adenocarcinoma and adenoacanthoma. UPSC and CCC were diagnosed in 31/266 (12%) and 6/266 (2%) of the patients respectively. The median follow-up time was 79 months (range 3 to 133 months). 49% of the patients with UPSC or CCC died of their cancer compared with 31% in the adenocarcinoma + adenoacanthoma group (RH=2.25; p=0.0022). Strong expression of the mutated p53 gene product was significantly more common in the UPSC + CCC group than in the reference group (64% vs. 19%), (p<0.0001). In a Cox multivariate analysis including histopathological and clinical variables, UPSC and CCC were still significant predictors of survival (p<0.05). When nuclear grade was added to the analysis, UPSC + CCC as well as the degree of differentiation lost most of their prognostic impact. In a final multivariate analysis, DNA ploidy was found to be the strongest predictor of outcome besides age and clinical stage.