Data are emerging implicating Wnt signaling in ovarian tumorigenesis. We sought to review the current literature on the subject and discuss the pathway's potential role as a prognostic marker and therapeutic target. We conducted a systematic literature review of studies investigating the association between Wnt signaling and ovarian cancer. Search strategies included online searching of the MEDLINE database and hand searching of relevant publications and reviews. Additional reports were collected by systematically reviewing all references from retrieved papers. Twenty-nine papers were identified that directly investigate Wnt signaling and ovarian cancer. Mutations in the CTNNB1 gene that codes for β-catenin, the key effector in the pathway, are directly linked to carcinogenic transformation but are mostly found in ovarian endometrioid adenocarcinomas, a histologic subtype of epithelial ovarian cancer. These mutations, along with others, lead to deregulation of the pathway and transcription of target genes. Differences in various intra-and extracellular components of the Wnt pathway have been demonstrated between normal ovarian and cancer cell lines and between benign tissue and ovarian cancer. These differences implicate Wnt signaling in the molecular events that lead to ovarian cancer development despite the fact that gene mutations are uncommon. The data suggest that Wnt signaling plays a role in ovarian tumorigenesis. The exact mechanisms by which this occurs need to be further elucidated. Wnt signaling is probably involved via multiple, diverse mechanisms. Further research in this area is warranted. Keywords ovarian cancer; tumorigenesis; Wnt signalingOvarian cancer is the fifth leading cause of death from cancer in women and is the leading cause of death from gynecological cancer. In 2007, it is estimated that there will be 22,430 new ovarian cancer cases with 15,280 deaths in the United States(1). The disease has an insidious onset, often presenting with vague nonspecific symptoms such as increasing abdominal girth, early satiety, and a change in bowel and/or bladder habits(2). Most ovarian cancer presents as stage III or IV disease. Worldwide, less than 30% of those with advanced ovarian cancer survive 5 years after initial diagnosis(3). Epithelial ovarian cancers (EOCs) arise from the ovarian surface epithelium (OSE) and account for greater than 80% of all ovarian Address correspondence and reprint requests to: Troy A. Gatcliffe, MD, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California-Irvine Medical Center, 101 The City Drive South, Building 56, Suite 260, Orange, CA 92868, USA. Email: tgatclif@uci.edu. Publisher's Disclaimer: This PDF receipt will only be used as the basis for generating PubMed Central (PMC) documents. PMC documents will be made available for review after conversion (approx. 2−3 weeks time). Any corrections that need to be made will be done at that time. No materials will be released to PMC without the approval of an author. Only t...