Objective: to compare the time course of changes in CA125 and epididymis protein 4 (HE4) while monitoring patients with ovarian cancer (OC). Materials and methods. Serum CA125 and HE4 levels were estimated in 76 patients with OC; among whom, serous adenocarcinoma was verified in 69 patients; endometrioid adenocarcinoma was diagnosed in 4, mucinous carcinoma in 1, and mixed serous-endometrioid adenocarcinoma in 2. Out of the 76 patients, 6 were found to have Stage I OC; 2, 41, and 27 had Stages II, III, and IV, respectively. The patients’ mean age was 53.8 years (20—74 years) before treatment. CA125 and HE4 values were compared at all stages of patient monitoring: a) prior to treatment; b) during neoadjuvant (preoperative) chemotherapy (CT); c) before surgery; d) 3 weeks after surgery; e) during adjuvant CT; f) in remission; g) in recurrence; h) during recurrence treatment. The markers were investigated before each cycle of CT. The discriminant level (DL) of 35 ng/ml was used for CA125.The age-dependent DLs were for HE4: <70 pmol for patients less than 40 years of age; <100 pmol for those aged 40—50 years, and <120 pmol for those over 50 years of age [36]. Results. At the start of treatment, the diagnostic sensitivity of the markers was high and similar (96.2% for CA125 and 92.3% for HE4). When a recurrence occurred, it reduced: CA125 and HE4 were higher only in 79.5 and 46.2% of cases, respectively. Analysis of rank correlation coefficients between the two markers confirmed that there were differences in CA125 and HE4 responses to the course of a tumor process. Thus, at the start of treatment, there was a moderate positive correlation between the levels of the markers levels (K=0.53). The correlation coefficient decreased to 0.37 and 0.06 during neoadjuvant chemotherapy and after surgery, respectively. In case of a verified recurrence, the correlation coefficient proved to be lower than at the start of treatment — 0.34 and then dropped to 0.13 after termination of recurrence treatment. By and large, the markers began to respond nonsimultaneously to the development of a recurrence in a considerable number of cases (44%) during monitoring: in 22% of the patients, CA125 increased 2—3 months earlier than HE4 and, on the contrary, in 22% of the patients, HE4 responded earlier than CA125. The proportion of cases of a simultaneous increase in both markers was 56%. Conclusion. Thus, there is evidence suggesting that it is expedient to introduce the additional marker HE4 when monitoring patients with OC. The application of the two markers will be able to give a more comprehensive idea of the tumor process at the stages of treatment and follow-up in a number of patients with OC.