Abstract: Exosomes have been intensively studied in recent decades. A liquid biopsy can detect exosomes as well as circulating freeDNA (cfDNA) and circulating tumor cells (CTCs). For osteosarcoma and Ewing sarcoma, which are derived from mesenchymal tissue, tumor heterogeneity can significantly affect the role of circulating tumor cells for monitoring prognosis based on the selected cell markers. This limitation has caused attention on exosomes derived from the maternal tumor cells because of the presence of maternal proteins and genes. The exosomes carrying their maternal partial functional proteins and genes may have an effect on tumorigenesis, andtheir detection may be beneficial for the diagnosis and treatment of osteosarcoma and Ewing sarcoma. This article reviews advancesin knowledge on the exosome properties, the effect of exosomes on malignant tumorigenesis, and their clinical application. The datawill provide a reference for clinical practitioners.