The purpose of the study was to examine menstrual cycle variabilities of Human Epididymis Protein 4 (HE4), serum levels in women with benign ovarian pathology. Prospective study was performed at the University clinic of obstetrics and gynecology in Skopje. Ninety four patients divided in two groups: 37 patients with ovarian endometriosis and 57 patients with “other benign pelvic masses” were included in the study. After ultrasound finding of a pelvic mass with a possible ovarian origin, all patients were serum sampled for HE4 and CA125. All cases underwent surgical removal of the mass with subsequent histologic evaluation which was referent for the group classification. There are not significant differences in HE4 blood levels between follicular (FP) and luteal phase (LP) in patients with ovarian endometriosis t (35) = 0.147, p = 0.884 and “other benign pelvic masses”, U = 424.5; p = 0.730. No significant differences in HE4 serum levels in follicular phases between the two groups, U = 222.0; p = 0.266 and in luteal phase significantly different HE4 serum levers between the two groups, (Mdn 40.20 vs. 35.50 pmol/L), U = 469.5; p = 0.048. HE4 is a robust biochemical marker and could be tested irrespective of the menstrual cycle.