5542 Background: Given the low prevalence of ovarian cancer, a successful strategy for early detection will require both high sensitivity (>90%) and specificity (99.6%) to achieve a positive predictive value of 10%. The requisite specificity might be attained through a two stage strategy that utilizes an abnormal value for serum marker(s) to prompt the performance of transvaginal sonography (TVS) in a limited number (2–5%) of women, reducing the specificity required for serum markers to 95–98%. Optimal sensitivity might be achieved by combining CA125 with other biomarkers. Methods: A training set from MDACC that included serum samples from patients with epithelial ovarian cancer (22 stage I and 19 stage II), 40 with benign disease and 99 healthy individuals, was analyzed using the CA125II immunoassay and SELDI-TOF-MS protocols to measure 7 proteins [transthyretin, Apo-A1, transferrin, hepcidin, s2M, CTAP3, and ITIH4]. Using normalized peak intensity data, statistical models were fit by logistic regression...