The ability to differentiate a malignant from a benign ovarian mass was assessed for four diagnostic procedures: serum CA 125, clinical examination, original ultrasound, and reviewer ultrasound interpretation. When these tests were used individually, the sensitivity and specificity of CA 125 levels were equal to those of a review ultrasound. Overall, the sensitivity of clinical impression and original ultrasound was poor. Sensitivity and specificity were highest for CA 125 assays in postmenopausal patients, especially when these were used as the second diagnostic test. Positive and negative predictive values significantly increased among postmenopausal patients when CA 125 was added to any of the other diagnostic tests examined. In conjunction with such tests, measurement of serum CA 125 significantly increased diagnostic accuracy and may thus have an important role in the preoperative evaluation of women with ovarian masses.