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In the era of precision medicine, the growing number of predictive biomarkers have modified the clinical paradigm for advanced tumor patients. Standard tissue specimens are often limited for comprehensive genomic profiling for testing biomarkers. Liquid biopsy became a milestone in clinical stratification of advanced tumor patients integrating tissue based molecular analysis. International societies routinely approved peripheral blood integrating genomic profile of actionable biomarkers but unexplored scenarios expanding potential applications are under investigations. Within the term liquid biopsy, we include each biological fluid where circulating free DNA and beyond (circulating tumor cells, extracellular vesicles, tumor-educated platelets, and microRNAs) may be isolated.