However, it is now increasingly recognized that NRF2 can exert oncogenic as well as oncosuppressive functions, so that the development of effective therapeutic approaches based on NRF2 modulation requires a careful evaluation of the specific context of its activation including not only the histotype, stage, and genetic background of a specific tumor but also the therapeutic scheme of administration and the target population that might benefit from treatment. This evidence concerns the gene NFE2L2 and neoplasm.