Objectives: In order to improve the early diagnosis of ovarian cancer (OC), we evaluated human epididymis secretory protein 4 (HE4), the risk of malignancy index (RMI), the risk of ovarian malignancy algorithm (ROMA), and the Copenhagen Index (CPH-I) in their ability to predict the risk of adnexal masses being malignant, and in discriminating between serous and mucinous ovarian tumors. Methods: A study consisting of 509 patients who were diagnosed with benign, borderline, and malignant adnexal tumors was conducted. We analyzed the values of HE4, RMI, ROMA, and CPH-I. In addition, CA125, CEA, CA125/CEA ratio, CA199, and CA125/CA199 ratio were also assessed to determine their predictive values to diagnoses serous or mucinous ovarian tumors. Results: To differentiate between benign and borderline ovarian tumors, we evaluated RMI and CPH-I scores which showed high AUC (0.7593, and 0.7128, respectively), but neither of them showed both high sensitivity and specificity. When discriminating benign and malignant tumors, RMI and CPH-I performed the best for premenopausal women; whereas ROMA and HE4 performed the best for postmenopausal women. Patients with values above the cutoff for CA125 (> 328.3 U/mL), CA125/CEA (> 82.26), and CA125/CA199 (> 5.633), were more likely to be diagnosed with serous carcinoma. Whereas those with higher values for CEA (> 3.7 \mug/L) and CA199 (> 27.81 ng/mL) were more likely to have a mucinous carcinoma. Conclusion: RMI and CPH-I for premenopausal women, ROMA and RMI for postmenopausal women were reliable indicators to differentiate between women with benign versus malignant tumors. In addition, the ratios CA125/CEA and CA125/CA199 could be used to distinguish serous from mucinous ovarian carcinomas.