Abstract Objective Uterine papillary serous carcinoma (UPSC) is a clinically and pathologically distinct subtype of endometrial cancer. Although less common than its endometrioid carcinoma (EEC) counterpart, UPSC accounts for a disproportionate number of endometrial cancer related deaths. To date, limited prospective trials exist from which evidence-based management can be developed. This review summarizes the available literature concerning UPSC in an effort to provide the clinician with information pertinent to its management. Methods MEDLINE was searched for all research articles published in English between January 1, 1966 and May 1, 2009 in which the studied population included women diagnosed with UPSC. Although preference was given to prospective studies, studies were not limited by design or by numbers of subjects given the paucity of available reports. Results UPSC is morphologically and genetically different from EEC. Women often present with postmenopausal vaginal bleeding, but may also present with abnormal cervical cytology, ascites, or a pelvic mass. In some cases, the diagnosis may be made with endometrial biopsy, while in other cases it is not made until the time of definitive surgery. Metastatic disease is common and best identified via comprehensive surgical staging. Local and distant recurrences occur frequently, with extra-pelvic relapses reported most commonly. Optimal cytoreduction and adjuvant platinum/taxane-based chemotherapy appear to improve survival, while adjuvant radiotherapy may contribute to loco-regional disease control. Conclusions Women diagnosed with UPSC should undergo comprehensive surgical staging and an attempt at optimal cytoreduction. Platinum/taxane-based adjuvant chemotherapy should be considered in the treatment of both early- and advanced-stage patients. Careful long-term surveillance is indicated as many of these women will recur. Prospective clinical trials of women with UPSC are necessary in order to delineate the optimal therapy for women with newly diagnosed and recurrent disease.