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Differentiation between benign and malignant ovarian neoplasms is essential to create a system for patient referrals. Therefore, tumor markers such as CA-125 and human epididymis protein 4 (HE-4) as well as the risk ovarian malignancy algorithm (ROMA) and risk malignancy index (RMI) values were considered individually and in combination to evaluate their utility in referral of women at a high risk of having an ovarian malignancy to cancer centers where multidisciplinary input is available. Patients who were diagnosed with an adnexal mass through imaging analyses or clinically (n = 35) were assessed for their expression of the tumor markers CA-125 and HE-4 and were finally compared to the histopathology of the tumor after surgery which has been taken as the gold standard. The ROMA and RMI values were also determined. The sensitivity, specificity, PPV, NPV, PLR and NLR of each parameter were calculated. Two different sets of analysis were made: one including benign and borderline masses together and the other including malignant and borderline masses together. The sensitivity of ROMA (91%) was highest when compared to RMI, CA-125 and HE-4. Specificity and positive likelihood ratio of HE-4 were highest at 87.5% and 5.1, respectively, when compared to all other parameters considered in our study. CA-125 had the least sensitivity and specificity (45 and 54%, respectively). Diagnostic accuracy of all the parameters was better in diagnosing malignant lesions than borderline tumors. Diagnostic accuracy using ROMA was better than RMI in differentiating malignant from benign lesions. Determination of HE-4, CA-125, RMI and ROMA algorithm was not helpful in differentiating patients with borderline tumors from benign lesions. ROMA had the best sensitivity of all the parameters considered.