In the latest revision of the “hallmarks of cancer”, Hanahan [88,89] introduced epigenetics as a hallmark of carcinogenesis [90] and further classified it into three categories: (a) TME mechanisms that drive epigenetic changes, such as the influence of hypoxia in the ten-eleven translocation (TET) demethylase, and of zinc finger E-box-binding homeobox 1 (ZEB1), a modulator of EMT, in histone methyltransferase SET domain-containing 1B (SETD1B); (b) epigenetic changes causing intratumoral heterogeneity; and (c) epigenetic regulation of tumor-related stromal cells [90]. The gene discussed is ZEB1; the disease is cancer.