Liquid biopsy in cancer is a revolutionary diagnostic concept defined by the analysis of biological material of tumor origin that extravasate to body fluids. Most common liquid biopsy studies use circulating tumor cells (CTCs) or circulating tumor-derived factors, in particular, circulating tumor DNA (ctDNA)(Alix-Panabières and Pantel, 2016; Perakis and Speicher, 2017). In the last 5 years, cutting-edge technologies such as next-generation sequencing (NGS) or digital PCR (dPCR) have been applied to detect blood-based, tumor-specific biomarkers such as CTCs and ctDNA (Husain and Velculescu, 2017; Pantel and Alix-Panabières, 2019). The quantification of circulating DNA molecules or CTCs showed per se prognostic value in many cancers (Haber and Velculescu, 2014). Besides this immediate analysis, another advantage of these biomarkers resides in the possibility of testing specific mutations, methylation profiles, and other DNA patterns (cfDNA and CTCs) and alternatively, proteins and the possibility of generating patient-derived xenografts (PDX) from the most aggressive cells in the tumor that putatively could initiate metastatic outgrowth (CTCs). Furthermore, the development of high sensitivity and specificity techniques enabled the identification of minimal residual disease (MRD) in cancer patient’s follow-up blood samples (Pantel and Alix-Panabières, 2019). Complementary to these biomarkers, extracellular vesicles (EVs) are emerging as powerful biomarkers to provide information about the tumor and the systemic changes occurring during the disease. EVs are a broad and heterogenous group of vesicles secreted by almost any kind of cell that display a wide range of sizes (30 nm− 5µm in diameter Witwer and Théry, 2019) and are composed of a lipid bilayer enclosing nucleic acids, proteins, lipids, metabolites (Colombo et al., 2014). EVs are considered as a mechanism of cellcell communication regulating paracrine and distal cell communication (Tkach and Théry, 2016). According to this, EVs have been detected in most biological fluids (Wiklander et al., 2019). The isolation of EVs allows for the subsequent analysis of their content that is defined by the cell of origin of the vesicle. Due to their heterogeneous content (protein, nucleic acids, lipids, metabolites, etc.), their ubiquitous production by body cells and detection in most biological fluids, circulating EVs could be useful for specific or multiplatform analyses to provide an accurate evaluation of cancer disease at early time points, during progression, therapy and post-treatment facilitating the detection of minimal residual disease and relapse anticipation (LeBleu and Kalluri, 2020).