BACKGROUND: The goal was to evaluate human epididymis protein 4 (HE4) in epithelial ovarian cancer diagnosis and preoperative staging. PATIENTS AND METHODS: All females presented in the period from 1/3/2018 to 1/3/2019 to the National Cancer Institute -Cairo University with an adnexal mass and had initial serum tumour marker levels and pathology documented. We collected Patients' data from hospital records. Statistical analysis and data correlations were done to compare HE4 with pathological type and stage and with other markers. RESULTS: We included 111 females. Forty-five patients were diagnosed with EOC. Postmenopausal HE4 was statistically significant, with the area under curve (AUC) 0.711 and p-value 0.005.HE4 showed a sensitivity of 68.2% and specificity of 60 %, PPV of 83.3%, NPV of 56.3%, and total accuracy of 70.6% by using a cut-off value of 64.6 Pmol/L. For premenopausal women, HE4 was statistically insignificant. Higher levels of preoperative HE4 were associated with advanced stages of EOC (III, IV) more than early stages. CONCLUSION: HE4 represents a promising marker of EOC. It does not show high levels in benign conditions. Preliminary results indicate that HE4 can play a role in the diagnosis and preoperative staging of EOC.