The recent identification of a seven-transmembrane receptor namely GPER (G protein estrogen receptor, formerly GPR30), which is able to mediate the estrogen action, has suggested a further mechanism through which estrogenic compounds may induce relevant biological responses in both tumor cells and important components of the surrounding microenvironment like cancer associated fibroblasts (CAFs) [35–44]. The gene discussed is GPER1; the disease is cancer.