Prognostic value of indoleamine 2,3-dioxygenase expression in high grade osteosarcoma. Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolising enzyme inducing immune tolerance. Some reports have noted a clinical correlation between IDO expression and outcome in some malignant tumors. This study aimed to investigate IDO expression as related to prognosis in osteosarcoma. IDO expression was immunohistochemically scored as five grades. IDO was expressed in most of the cases. Univariate analysis revealed no significant correlation between IDO staining intensity and various variables including sex, age, anatomical site, chemotherapy regimen, necrosis after chemotherapy, and surgical stage. Patients with high IDO expression had significantly lower metastasis-free survival (P = 0.016) and overall survival (P = 0.005). On univariate analysis, age over 20 years and high IDO expression were found to be independent risk factors of lower overall survival and metastasis-free survival. On multivariate analysis, there was no significant correlation between high IDO expression and metastasis-free survival (P = 0.070) and overall survival (P = 0.066). The immune tolerance mediated through IDO may have an important role in the tumorigenesis of osteosarcoma and may exert an impact on the clinical outcome, and thus may lend itself as a therapeutic target of immunotherapy for osteosarcoma.