In order to shed more light on the influence of Nrf2 signaling in human ccRCC, we assessed Nrf2 gene mutations, the rs6721961 SNP, and Nrf2 protein expression in patients with metastatic ccRCC, as well as associations with the response to adjuvant vascular endothelial growth factor (VEGF)-targeting therapy and survival. This evidence concerns the gene NFE2L2 and nonpapillary renal cell carcinoma.