This study was conducted to determine and compare the sensitivity, specificity, PPA and NPV of Mesothelin tumor marker, CA-125, combination of Mesothelin and CA-125 as a tumor marker in patients with epithelial ovarian carcinoma. This is a cross sectional diagnostic test on 30 subjects with Malignant dan 30 sunjects with benign ovarian tumors that meet the inclusion and exclusion of research criteria in Department of Obstetrics and Gynecology, Medical Faculty Airlangga University/Dr. Soetomo, Surabaya. Blood sample were taken prior to surgery to examine tumor markers (Mesothelin and CA-125) and ultrasound to evaluate tumor mass, and then histopathology of surgery specimen. Statistical data calculated using SPSS. There is a significant increase of Mesothelin serum level and can be used as a tumor marker (alone or in combination with other methods as a triage tool, consider the use of new cut-off value of 1.75 nmol/L). Sensitivity, specificity, PPV, NPV of CA125 is 70%, 33.3%, 51.2% and 52.6%. Sensitivity, specificity, PPV, NPV of Mesothelin-1 is 50%, 80%, 71.4% and 61.5%. Sensitivity, specificity, PPV, NPV of Mesothelin-2 is 36.7%, 93.4%, 84.6% and 59.6%. Sensitivity, specificit , PPV, NPV combination of CA-125 + Mesothelin-1 is 33.3%, 86.7%, 71.4%, 56.5% and 60%. Sensitivity, specificity, PPV, NPV combination of CA-125 + Mesothelin-2 is 23.3%, 93.3%, 77.8%, and 54.9%. Sensitivity, specificity, PPV, NPV of RMI is 83.3%, 36.7%, 56.8%, and 68.8%. CA-125 (as a single tumor marker) has the highest sensitivity and proved as a simple and effective method for the early detection at general population. Mesothelin-2 (either as a single tumor marker or in combination) is more appropriate for the diagnosis tools (triage, determining the risk of Malignant from benign ovarian masses) are better than the current and can be considered to replace CA-125.