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Summary: The tumor microenvironment encompasses an intertwined ensemble of both transformed cancer cells and non-transformed host cells, which together establish a signaling network that regulates tumor progression. By conveying both homo- and heterotypic cell-to-cell communication cues, tumor-derived extracellular vesicles (tEVs) modulate several cancer-associated processes, such as immunosuppression, angiogenesis, invasion, and metastasis. Herein we discuss how recent methodological advances in the isolation and characterization of tEVs may help to broaden our understanding of their functions in tumor biology and, potentially, establish their utility as cancer biomarkers.