Objective: The aim of the study was to evaluate the effectiveness of HE4 alone and in combination with CA125 (ROMA) in selecting patients at high risk of adnexal malignancy. Material and methods: Serum CA125 and HE4 levels were determined and the ROMA value was calculated in 259 women qualified for surgery due to adnexal mass. The results were compared with histopathological findings. Results: Sensitivity and specificity in preoperative diagnosis of primary ovarian cancer were 93.2% and 71.5% for CA125 and 95.4% and 81.3% for HE4, respectively. ROMA algorithm achieved sensitivity of 95.4% and specificity of 79.8%. All methods reached sensitivity of 100% at specificity of 65.6% for CA125, 93.4% for HE4 and 82.0% for ROMA in premenopausal women, whereas in postmenopausal women sensitivity and specificity achieved levels of 92.1% and 81.7% for CA125, 94.7% and 60.6% for HE4 and 94.7% and 76.1% for ROMA, respectively. Serum levels of both CA125 and HE4 were significantly higher in women with primary ovarian cancer as compared to benign disease. Concentrations of CA125 in patients with endometriosis were significantly elevated as compared to women with other benign tumors. Such relation was not observed when HE4 levels were concerned. Conclusions: CA125, HE4 and ROMA are useful in preoperative diagnosis of ovarian malignancy. HE4 improves the diagnostic accuracy in cases of endometriosis, verifying false positive results of CA125.