Background and Objectives: Endometriosis is a benign gynecological disease that displays symptoms and pathophysiological features similar to ovarian carcinoma.CA-125, a well Known biomarker of ovarian malignancy often shows false positive results in Endometriosis resulting many women undergo unnecessary surgery. The aim of our study is to evaluate utility of HE4, ROMA to differentiate endometriosis from ovarian cancer. Methodology: 90 Women having adnexal mass with suspected malignancy on imaging (Ultrasound) anticipated to go for surgery were chosen as patients. Taking Biopsy as gold standard patients were divided into Endometriosis, benign pathology and malignant group.Levels of biomarkers CA-125 and HE4 were analysed, Risk of malignancy algorithm (ROMA) was calculated and compared with histopathology report. Sensitivity, Specificity and Area under Curves were evaluated. Results: Levels of HE4 and ROMA showed a significant increase only in malignant cases (p≤0.001). But, did not increase significantly in cases with endometriosis and benign pathology (p≥0.05). Thus, HE4 and ROMA can differentiate endometriosis patients from malignant patients. On the other hand, CA-125 showed a significant increase in malignant as well as endometriosis cases compared to benign pathology (p≤0.001) but did not showed statistical significant difference between Endometriosis vs. malignant (p≥0.05).HE4 and ROMA showed specificity of (90.9%) more than CA-125 (54.5%). The Area under Curve of HE4 and ROMA was (0.975 and 0.972) respectively was more than CA-125 (0.753) for distinguishing endometriosis from ovarian malignancy.