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Introduction Comprehensive analyses using clinical sequences subcategorized osteosarcoma (OS) into several groups according to the activated signaling pathways. Mutually exclusive co-occurrences of gene amplification ( PDGFRA/KIT/KDR, VEGFA/CCND3, and MDM2/CDK4 ) have been identified in approximately 40% of OS, representing candidate subsets for clinical evaluation of additional therapeutic options. Thus, it would be desirable to evaluate the specific gene amplification before starting therapy in patients with OS. Materials and Methods This is a retrospective study. We examined 13 cases of clinical OS samples using NanoString-based copy number variation (CNV) analysis. Decalcification and chemotherapeutic effects on this analysis were also assessed. Results First, the accuracy of this system was validated by showing that amplification/deletion data obtained from this system using various types of cancer cell lines almost perfectly matched to that from the Cancer Cell Line Encyclopedia (CCLE). We identified potentially actionable alterations in CDK4/MDM2 amplification in 10% of samples and potential additional therapeutic targets ( PDGFRA/KIT/KDR and VEGFA/CCND3 ) in 20% of samples, which is consistent with the reported frequencies. Furthermore, this assay could identify these potential therapeutic targets regardless of the sample status (frozen vs formalin-fixed paraffin-embedded [FFPE] tissues). Conclusion We established a NanoString-based rapid and cost-effective method with a short turnaround time (TAT) to examine gene amplification status in OS. This CNV analysis using FFPE samples is recommended where the histological evaluation of viable tumor cells is possible, especially for tumors after chemotherapy with higher chemotherapeutic effects.