Prior to the introduction of neoadjuvant chemotherapy in the comprehensive treatment of malignant bone tumors, the exact efficacy of chemotherapy in malignant bone tumors was not scientifically evaluated, and most of its efficacy was confirmed by clinical practice results. It is not certain which drug is more effective in the postoperative combination chemotherapy. Chemotherapy regimens can only be designed based on previous estimates. The introduction of neoadjuvant chemotherapy provides a basis for scientific assessment of drug sensitivity to tumors. This can be assessed specifically by clinical, imaging, and laboratory tests as well as by histological grading of postoperative tumor cell necrosis. Clinical assessment is based on whether the patient’s subjective symptoms are reduced by chemotherapy, especially pain relief and improvement of general condition. Clinical examination is based on whether the tumor volume is reduced, whether the boundary with normal tissue is clear, whether the edema reaction zone around the tumor is reduced, and whether the mobility of adjacent joints is improved. If Ewing sarcoma has a history of increased blood sedimentation and fever, it should also be included as a clinical index to observe the efficacy of treatment. In terms of imaging, whether the calcification and ossification of tumor increase, whether the boundaries of soft tissue mass shadow are clear, whether the size of the mass is reduced and whether the boundaries between the mass and normal bone are clear in the comparison of X-ray plain film before and after chemotherapy. Enhanced CT and angiography to show whether the tumor neovascularization is reduced or disappeared are objective indicators to observe the efficacy of treatment. MRI examination can show whether the tumor soft tissue is reduced, the boundary with surrounding tissue and necrosis. In the laboratory examination of osteosarcoma, whether alkaline phosphatase and lactate dehydrogenase decrease is also one of the indicators to observe the efficacy. Comparison of isotope bone scan results before and after chemotherapy showed that the degree and extent of radionuclide concentration was also an important indicator to observe the efficacy of chemotherapy. Among them, the isotope thallium 201 (Ti) is currently considered to be the most effective. The most important, sensitive and objective criterion for assessing the efficacy of preoperative chemotherapy is the histological response of the tumor to the chemotherapeutic agent. Proper assessment is essential for the development of postoperative chemotherapy regimens. This assessment requires the active participation of pathologists and the completion of a significant amount of work. They have to take specimen photographs of the resected tumor specimens and then take them according to the lattice graphic method developed by the Sloan-Kettering Cancer Center to determine the individual tissue sections for microscopic assessment of the efficacy of neoadjuvant chemotherapy. The number of lattices and sections depended on the size of the tumor, the assessment criteria according to the histological grading of tumor response to chemotherapy developed by Huvos et al. Grade I: almost no tumor cell necrosis; Grade II: mildly effective chemotherapy with reduced number of tumor cells, necrosis rate > 60%, and some areas with surviving tumor cells; Grade III: effective chemotherapy with tumor cell necrosis rate > 90% and very few surviving tumor cells; Grade IV: total tumor cell necrosis with no surviving tumor cells. According to the neoadjuvant chemotherapy data from Sloan-Kettering Cancer Center, 20% of the patients were grade IV, 21% were grade III, 29% were grade II, and 20% were grade I chemotherapy response. According to this assessment, for chemotherapy response grade III or IV, the preoperative chemotherapy regimen can be followed after surgery; for grade I and II, the chemotherapy regimen should be changed after surgery to shorten the chemotherapy interval and use more potent drugs. It has been shown that whether the lesion is located in the distal femur, proximal tibia, or proximal humerus-the three most common sites for osteosarcoma-there is no significant difference in their response to chemotherapy.