The HE4 protein, which belongs to the “ four disulfi de ” acid protein group, has emerged as one of the most promising biomarkers in gynecologic oncology. An expert meeting on the analytical and clinical performance of the quantitative determination of HE4 was held in November 2011, involving 25 clinical and laboratory specialists from 16 European countries.The aim of the meeting was to present and discuss the results of recent studies on the use of HE4 and on the Risk of Ovarian Malignancy Algorithm (ROMA), which combines the results of HE4 and CA 125. The meeting was structured in separate sessions focusing on ovarian cancer risk stratification, differential diagnosis, prognosis and monitoring and with diagnosis and monitoring of endometrial cancer. We present here a summary of the data and evidence, presented, together with consensus statements on the different topics, where available,and suggestions for further studies and evaluations required to establish optimal use of HE4, either alone or in combination with other markers, for diagnostic and prognostic purposes in gynecological malignancies. Available evidences support the utility of this new cancer biomarker for risk stratification,prognosis and monitoring of epithelial ovarian cancer and of endometrial cancer.