Uterine papillary serous carcinoma (UPSC) accounts for 10% of endometrial carcinomas but a higher proportion of deaths due to its aggressive nature and poor response to chemotherapy and radiotherapy. In order to add to the knowledge of UPSC in the literature and to review our local practices, we examined the pathology, medical records, and management of all cases of UPSC (67 patients) treated in South East Scotland over a 10-year period and also evaluated the prognostic significance of the percentage of UPSC in endometrial pipelle and hysterectomy specimens. Although only 63% of initial diagnostic biopsies were reported to contain UPSC, rereview of the cases revealed UPSC in 98.5% of the preoperative biopsies. The percentage of UPSC in the tumors did not affect the outcome. Stage, positive omentum, and treatment with external-beam +/- intracavitary radiotherapy were significantly correlated with overall survival and progression-free survival by univariate analysis, but only stage (P <0.01) was correlated with outcome on multivariate analysis. Chemotherapy did not affect outcome. UPSC may be difficult to diagnose in preoperative biopsies, particularly when present as part of a mixed tumor. Even a small percentage of UPSC in a diagnostic biopsy or hysterectomy specimen is correlated with a poor prognosis. This study emphasizes the need of a cooperative, prospective study on this distinct uterine carcinoma.