In this study, we profiled promoter-region DNA methylation in 265 ccRCC primary tumors and 133 adjacent tissues with Illumina HumanMethylation450 from The Cancer Genome Atlas data (TCGA), and found that a CpG-based biomarker (cg11201447, cg25247520, cg13309012, cg08995609) can efficiently distinguish ccRCCs from adjacent tissues and that RAB25 is hypermethylated in ccRCC tissues. This evidence concerns the gene RAB25 and nonpapillary renal cell carcinoma.