Ovarian cancer is the leading cause of gynecological malignancy-related mortality. CA125 level in patients with Epithelial Ovarian Cancer (EOC) and endometrioma can frequently be high. CA72-4 level was also elevated in several carcinomas including ovarian cancer. Due to its lack of specificity, however, this marker has a limited role in the differential diagnosis between EOC and endometrioma. In this research, we studied the levels of biomarkers CA125 and CA72-4 to determine their potential role in the differential diagnosis of endometrioma and EOC. For this goal, biomarkers CA125 and CA72-4 were identified in 75 patients with ovarian cancer and 75 patients with endometrioma. Cut-off levels for CA125 and CA72-4 were considered 35 U/ml and 3.8 U/ml, respectively. The data have been analyzed by SPSS, with a p-value<0.05 considered significant. Both markers CA125 and CA72-4 were remarkably elevated in EOC (p=0.001). Areas under the ROC curve for CA125 and CA72-4, with sensitivity of 0.48 and specificity of 0.52, were 0.633 and 0.624, respectively. The differences were not significant. It has been shown that CA125 and CA72-4 serum levels are elevated in patients with EOC; however, this did not lead to detection of malignancy. This means that CA72-4 level does not demonstrate a significant difference in malignancy diagnoses when compared to the use of CA125 alone.