Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Nearly 10 million women in the US are at high risk for EOC with greater than 21,000 new annual diagnoses. Over 60% of diagnosed patients have advanced stage EOC, with a five-year survival rate less than 30%, compared to over 90% five-year survival for localized disease. Stage I EOC is difficult to detect amid non-specific symptoms that delay workup until a pelvic mass is found. Once an adnexal mass is found, the current diagnostic armamentarium includes sonographic grading of the tumor and analyzing serum levels of tumor markers, Cancer Antigen 125 [CA-125] and Human epididymis protein 4 [HE4]. HE4 is reported to be the most sensitive biomarker for detecting stage I EOC, while elevated serum levels of CA-125 (e 35 U/mL) alone lack adequate sensitivity and specificity for a definitive diagnosis. HE4, measurable in urine, to our knowledge, has not been measured in peritoneal fluid, although culdocentesis has been a useful technique in the field of gynecology for many years and can be performed in an outpatient setting. A minimally invasive, reliable diagnostic tool is needed for poor surgical candidates to avoid an oophorectomy for benign disease that could result in unnecessary morbidity. Specific Aim: To determine if levels of tumor markers (CA-125 and HE4) and cytology from peritoneal washings obtained via the cul-de-sac correlate with a diagnosis of epithelial ovarian cancer. We hypothesize that measuring these markers in combination from peritoneal fluid may increase the sensitivity to the presence of cancer cells beyond the ovarian cortex which may result in earlier detection of EOC. Study design: The prospective study will recruit and consent a convenience sampling of 60 women scheduled for surgical staging of a suspicious adnexal mass. Surgical staging of endometrial and ovarian carcinomas includes the collection of peritoneal washings. Our innovative technique differs from standard culdocentesis by infusing saline into the cul-de-sac and re-aspirating for collection (i.e. peritoneal washings). Cytology of peritoneal aspirations will be analyzed along with levels of tumor markers, CA-125 and HE4. Relevance: Our research goal is to develop a simple, non-surgical diagnostic tool that could reliably identify EOC prior to surgical staging. Th decision to undergo an oophorectomy for benign disease may result in unnecessary morbidity in patients who are poor surgical candidates. Study results could change the current clinical paradigm: operative management of a potentially benign tumor to avoid delayed surgical intervention of a potential malignancy. The proposed efforts will, at the very least, help answer the potential utility of clinic- based, non-surgical culdocentesis in pelvic mass triaging and ovarian cancer diagnosis. A minimally invasive, reliable diagnostic tool would improve early detection and, therefore, patient survival rates for EOC.