OBJECTIVES: To improve the poor survival in ovarian cancer (OC) patients, the research has been focused on new OC markers. One aim is to find markers to identify the cancers in early preclinical stages by screening. Another aim is to find new diagnostic markers, which may select patients at high risk for OC for quick referral to highly specialized centers in gynecologic oncology. These aims were addressed in the present study by evaluating serum tetranectin (TN) and serum CA125 on a large number of pre- and postmenopausal women with ovarian tumors and controls. METHODS: The potential ability of the markers to discriminate between the four groups (208 benign ovarian tumor, 153 borderline ovarian tumor (BOT), 445 OC and 1333 age matched controls) in OC screening was examined. We also constructed a risk assessment index (RAI) for discrimination between tumor groups based on these variables and menopausal status. RESULTS: Highly significant differences in both TN and CA125 levels were found between all the four groups as well as between the different FIGO stages of OC patients. A very high probability of having OC or a benign tumor, respectively, was predicted by the RAI. CONCLUSIONS: In the case-control part of the study, we found that TN and CA125 deserve to be validated on pre-clinical samples by inclusion in future marker panels. The RAI is also a potential new candidate for a diagnostic tool for selecting patients at high risk for having OC; hence it deserves further evaluation in a prospective clinical study.