The biological processes and detection methods of circulating nucleic acids and a schematic of liquid biopsy in sarcoma. Liquid biopsy includes the isolation of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and circulating tumor RNA (ctRNA) and exosomes from the blood. Clinical application of liquid biopsy in sarcoma involve diagnosis in the early stage, monitoring of sarcoma progression, (e.g., local recurrence and distant metastasis), prediction of prognosis and detection of response to therapy. The biological processes of circulating nucleic acids are shown in the magnified view in step 5, and ctDNA, ctRNAs, and exosomes can be discharged into the circulation by apoptotic or necrotic CTCs. Some of the circulating nucleic acids are degraded by the liver and kidney, and the remaining circulating nucleic acids can be detected and amplified by PCR and NGS, which can be used to monitor sarcomas. Bloodborne CTCs, ctDNA, ctRNAs and exosomes can be analysed to diagnose sarcoma, predict prognosis and evaluate response to therapy. This process is called “liquid biopsy”. Based on these steps, we can monitor the tumor. Abbreviations: CTCs: circulating tumor cells; ctDNA: circulating tumor DNA; ctRNA: circulating RNA; RBC: red blood cell