Abstract. Tumour markers are widely used for the diagnosis, staging and monitoring of colorectal cancer (CRC) patients in clinical practice. Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the most frequently used biomarkers in CRC patients. A number of studies have recently investigated the presence of human epididymis protein 4 (HE4) overexpression in certain cancer types. Its significance in ovarian and endometrial cancer has been well-demonstrated. The aim of the present study was to evaluate the significance of serum HE4 levels in CRC patients. A total of 46 newly diagnosed CRC patients and 36 age-and gender-matched healthy subjects were included in the study. The concentrations of CEA and CA19-9 were also determined and compared according to HE4 levels. HE4 positivity was determined in 13 of the 46 cases (28.3%) in the CRC group, but no HE4-positive subjects were identified in the control group (0%; P=0.009). The area under the receiver operating characteristic curve for HE4 positivity was 0.641 (95% CI: 0.523-0.760). HE4 was statistically significantly positive in patients with stage III-IV disease and in those with high CA