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Both adolescents and children suffer from osteosarcoma, localized in the metaphysis of the long bones. This is the most common primary high-grade bone tumor in this patient group. Early tumor detection is the key to ensuring effective treatment. Improved osteosarcoma outcomes in clinical trials have been contingent on biomarker discovery and an evolving understanding of molecules and their complex interactions. In this review, we present a short overview of biomarkers for osteosarcoma, and highlight advances in osteosarcoma-related biomarker research. Many studies show that several biomarkers undergo critical changes with osteosarcoma progression. Growing knowledge about osteosarcoma-related markers is expected to positively impact the development of therapeutics for osteosarcoma, and ultimately of clinical care. It has also become important to develop new biomarkers, which can identify vulnerable patients who should be treated with more intensive and aggressive therapy after diagnosis.