The purpose of this study was to determine the diagnostic value of CA 125 in comparison with transabdominal ultrasound (US) in the evaluation of postmenopausal women with pelvic mass to detect malignant epithelial ovarian tumors. Postmenopausal patients with pelvic mass were studied with gynecologic examination, US and CA 125 determination. Three hundred eighty-eight patients were entered in the study. According to stratification based on US (probably benign, equivocal, possibly malignant) and CA 125 (< 35 U/ml, negative; between 35 and 65 U/ml, borderline; > 65 U/ml, positive), 290 patients were considered eligible for surgery. Specificity, sensitivity, positive and negative predictive value, and accuracy of US and CA 125 were calculated with respect to histological examination. Out of 290 operated patients, 134 had a benign ovarian pathology, 34 had extraovarian benign pathology, 106 had an ovarian malignancy, and 16 presented with an extraovarian malignant pathology. The results according to ovarian malignant pathology were as follows. CA 125 (> 65 U/ml): Specificity, 92.5%; sensitivity, 71.7%; accuracy, 83.3%. CA 125 (> 35 U/ml): Specificity, 82.0%; sensitivity, 78.3%; accuracy, 80.4%. US: Specificity, 77.6%; sensitivity, 84.9%; accuracy, 80.3%. Combination of US and CA 125 (> 65 U/ml): Specificity, 96.1%; sensitivity, 91.7%; accuracy, 94.3%. Determination of CA 125 is a highly specific method in predicting ovarian cancer in postmenopausal women with a pelvic mass. The association with US significantly improves the overall accuracy and may support therapeutical decision making by distinguishing between a significant percentage of women most likely to benefit from prompt intervention and women who may be managed following minor surgical diagnostic approach, such as fine-needle aspiration.