The prevalence of germline mutations in known predisposition genes and other genes associated with cancer development was explored in 254 patients with advanced RCC; about 16% carried pathogenic or seemingly pathogenic germline variants at the level of 17 different cancer-predisposition genes: 5.5% of these patients carried mutations at the level of RCC-associated genes, such as FH, BAP1, VHL, MET, SDHA, and SDHB; 10.5% of these patients carried mutations in genes not clearly associated with RCC, including the CHEK2 gene [8]. This evidence concerns the gene VHL and cancer.