['To test the value of serum CA-125 measurements alone or as part of a multimodal strategy to distinguish between malignant and benign ovarian tumors before surgery based on a large prospective multicenter study (International Ovarian Tumor Analysis).', 'Patients with at least one persistent ovarian mass preoperatively underwent transvaginal ultrasonography using gray scale imaging to assess tumor morphology and color Doppler imaging to obtain indices of blood flow.', 'Data from 809 patients recruited from nine centers were included in the analysis; 567 patients (70%) had benign tumors and 242 (30%) had malignant tumors-of these 152 were primary invasive (62.8%), 52 were borderline malignant (21.5%), and 38 were metastatic (15.7%). A logistic regression model including CA-125 (M2) resulted in an area under the receiver operating characteristic curve (AUC) of 0.934 and did not outperform a published (M1) without serum CA-125 information (AUC, 0.936). Specifically designed new models including CA-125 for premenopausal women (M3) and for postmenopausal women (M4) did not perform significantly better than the model without CA-125 (M1; AUC, 0.891 v AUC, 0.911 and AUC, 0.975 v AUC, 0.949, respectively). In postmenopausal patients, serum CA-125 alone (AUC, 0.920) and the risk of malignancy index (AUC, 0.924) performed very well. Results were very similar when the models were prospectively tested on a group of 345 new patients with adnexal masses of whom 126 had malignant tumors (37%).'] Does inclusion of CA-125 improve mathematical models developed to distinguish between benign and malignant adnexal tumors?