HE4 is Human Epididymis Protein which is created by expression of HE4 (WFDC2) gene. It is a secretory protein of the WAP protease inhibitors, which is observable in ovarian cancer. Although discovered in 1991, and numerous studies on the topic of HE4 already exist, further research in the early stages of the disease is needed due to the exceptional histological complexity of EOC and uneven expression of markers in all EOC subgroups. Diagnostic significance of HE4 compared with CA-125 is in fact that it provides better able to distinguish the situation with benign tumors in comparison to the situation without the tumor and to serve for the monitoring and detection of return of ovarian cancer. Small concentrations of HE4 can be regarded as an indicator of disease remission. The aim of this paper is to systematically demonstrate the knowledge of current literature on the diagnostic significance of HE4 with ovarian cancer, as well as to demonstrate the published results of previous experimental and clinical research on its predictive impact on the outcome of the disease in different histological types of ovarian cancer and different stages of FIGO cancer classification. Material and methods: Using keywords (ovarian cancer, tumor, HE4, early detection,diagnosis, prognosis) the relevant scientific and technical literature data were accessed via a database browser (PubMed, BioMed Central, Medline, etc.), and the presentation of current knowledge about HE4 has been developed, as well as about its diagnostic significance in the early detection of ovarian cancer with special emphasis on the available technologies and methods for its diagnosis. Conclusion: The discovery of HE4 and its role as an independent marker or in combination with CA125 helped in the detection, diagnosis and prognosis of ovarian cancer. Despite numerous studies none of the markers (CA125, HE4, ROMA) is approved as a screening test for ovarian cancer, thus further research is needed.