Objective: To develop a cost-minimization analysis of a multivariate index assay (MIA) used for women with complex pelvic masses. Methods: A decision analysis model was used to evaluate 81,000 hypothetical patients with a complex pelvic mass requiring surgery. Three strategies were evaluated: (1) referral to a gynecologic oncologist (GO) based on clinical assessment including physical exam, ultrasonography, and CA125 (CLINICAL); (2) utilization of a multivariate index assay (MIA); or (3) referral of all patients to a GO (REFER ALL). Various reoperation rates were evaluated with sensitivity analyses. Actual payer costs were compared between each strategy. Results: The CLINICAL strategy cost $933.9 million (M) and resulted in 72% of patients receiving appropriate initial surgical staging. The REFER ALL strategy cost $939.7 M and all patients were appropriately staged. The MIA strategy cost $976.7 M and resulted in 91% of patients having appropriate initial staging. Using conservative reoperation rates (10-20%), 461 patients required reoperation using CLINICAL strategy compared to 142 patients in MIA strategy. Using aggressive reoperation rates (40-50%), 1715 patients required reoperation using CLINICAL strategy resulting in an incremental cost of $15.2 M compared to 529 patients at $4.7 M in MIA strategy. The increased costs associated with an aggressive reoperation rate resulted in the REFER ALL strategy being the least expensive alternative, with the highest rates of appropriate initial surgery. Conclusions: Utilizing an MIA resulted in more ovarian cancer patients receiving appropriate initial surgery, but at increased costs. Referring all patients with complex masses avoids the most reoperations at reduced cost compared to using an MIA. © 2012 Elsevier Inc. All rights reserved.