Despite all these clinical and experimental data showing the importance of estrogens in the development and progression of ovarian cancer, many questions still remain and, among these, the contribution of 17β-estradiol signaling through ERα, ERβ isoforms and GPER is likely to be really complex and specific to particular cell types, tissues, ligands and diseases, thus deserving additional studies. The gene discussed is ESR2; the disease is ovarian cancer.