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In this review, the key substances found in the blood, such as circulating free (cf)DNA, cfRNA, proteins, and exosomes (sacs containing proteins, DNA and/or RNA), which may act as biomarkers for monitoring the progression of clear cell renal cell carcinoma (ccRCC) are discussed. Limitations of these techniques and promising technologies that could help with the use of liquid biopsies for the prognosis of metastatic RCC are highlighted.