We examined the efficacy of CA125 and urinary gonadotropin fragment (UGF) measurements for differentiating benign from malignant pelvic masses. CA125, at a cutoff of greater than or equal to 35 U/ml, detected 82% (n = 71) of ovarian malignancies, but also falsely detected 14% of (n = 332) patients with benign pelvic masses. When the CA125 cutoff was raised from greater than or equal to 35 to greater than or equal to 200 U/ml, the number of false-positives decreased to 1.2%, a manageable level. However, using greater than or equal to 200 U/ml only 49% of cancers were detected. We examined levels of UGF and found that they complement those of CA125, detecting false-negatives. Using UGF at a cutoff of greater than 8 fmol/ml and CA125 at greater than or equal to 200 U/ml a combined sensitivity of 86% was achieved for malignant pelvic masses, with minimal false-detection of benign disease (less than 1.2%). We propose that parallel measurements of CA125 and UGF should be used for discriminating benign and malignant pelvic masses.