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Simple Summary  Liquid biopsies have emerged as a new tool for early diagnosis. In renal cell carcinoma, this need is also evident and may represent an improvement in disease management. Hence, in this review we discuss the most updated advances in the assessment of miRNAs in liquid biopsies. Moreover, we explore the potential of circulating or exosome miRNAs in renal cell carcinoma to overcome the tissue biopsies limitations.    Abstract  Renal cell carcinoma is the third most common urological cancer. Despite recent advances, late diagnosis and poor prognosis of advanced-stage disease remain a major problem, entailing the need for novel early diagnosis tools. Liquid biopsies represent a promising minimally invasive clinical tool, providing real-time feedback of tumor behavior and biological potential, addressing its clonal evolution and representing its heterogeneity. In particular, the study of circulating microRNAs and exosomal microRNAs in liquid biopsies experienced an exponential increase in recent years, considering the potential clinical utility and available technology that facilitates implementation. Herein, we provide a systematic review on the applicability of these biomarkers in the context of renal cell carcinoma. Issues such as additional benefit from extracting microRNAs transported in extracellular vesicles, use for subtyping and representation of different histological types, correlation with tumor burden, and prediction of patient outcome are also addressed. Despite the need for more conclusive research, available data indicate that exosomal microRNAs represent a robust minimally invasive biomarker for renal cell carcinoma. Thus, innovative research on microRNAs and novel detection techniques are likely to provide clinically relevant biomarkers, overcome current clinical challenges, and improve patient management.

Unveiling the World of Circulating and Exosomal microRNAs in Renal Cell Carcinoma