Although NFE2L2 is commonly known as tumour suppressor whose activation protects from cellular insults upon oxidative or electrophilic stress and is thus anti-tumourigenic and promotes cell survival of normal as well as pre-malignant cells, there is accumulating evidence for the’dark side of NFE2L2’: constitutive activation of NFE2L2 enhances survival, progression as well as chemo- and radioresistance also in cancer cells and thus potentially acting as an oncogene under certain circumstances. This evidence concerns the gene NFE2L2 and cancer.