Targeted sequencing was carried out using plasma cfDNA and ctDNAIn 30% patients, somatic mutations were detected in cfDNA. Most frequently detected mutations included TP53 (n = 6), BAP1 (n = 5), VHL (n = 5), TSC1 (n = 4), and SETD2 (n = 3.ccRCC patients with detectable ctDNA showed shorter fragment sizes of cfDNA.cfDNA fragments with SETD2, BAP1, and NF2 mutations were significantly shorter than wild type cfDNA fragments.Detectable ctDNA and cfDNA size associated with poor PFS and CSS (long vs. short, P = .004, P = .011 and high vs. low, P = .317, P = .127, respectively). This evidence concerns the gene SETD2 and nonpapillary renal cell carcinoma.