Objective: Uterine papillary serous carcinoma (UPSC) represents a distinct subtype of endometrial cancer. UPSC is less common than endometrioid carcinoma (ECC) but accounts for a disproportionate number of uterine cancer related deaths. This article critically reviews the literature pertinent to the pathology, pathogenesis, diagnosis, management, and outcome of patients with UPSC. Methods: MEDLINE was searched for all research articles published in English between January 1, 1967-January 1, 2012 which reported on patients diagnosed with UPSC. Given the rarity of this tumor, studies were not limited by design or number of reported patients. Results: UPSC represents a histologically aggressive subtype of endometrial cancer. It commonly presents with extra uterine disease involvement which can be identified by comprehensive surgical staging. Optimal cytoreduction and systemic platinum/taxane-based adjuvant therapy appear to confer a survival advantage. Conclusions: UPSC is a biologically distinct entity, different from ECC. Future studies should explore the role of targeted therapies in the management of UPSC. © 2012 Elsevier Inc. All rights reserved.