BACKGROUND Toll-like receptor (TLR) family members are part of the major pathogen-recognition system for innate immunity. TLR10, the only remaining orphan receptor with an unknown ligand, has been poorly studied in tumors, and its functional and clinical relevance are unclear. MATERIAL AND METHODS We analyzed TLR10 expression data in The Cancer Genome Atlas (TCGA) by established computational approaches (UALCAN, GEPIA, CGGA, and TIMER) and confirmed them by immunohistochemistry analysis. RESULTS Bioinformatics analysis showed that TLR10 was most highly expressed in diffuse large B cell lymphoma (DLBC), acute myeloid leukemia (LAML), and glioblastoma multiforme (GBM) patients. A data-mining study also revealed that TLR10 levels were positively correlated with WHO grade in glioma, and patients with high TLR10 levels showed shorter overall survival (OS) and disease-free survival (DFS) times than patients with low TLR10 levels. TISIDB and TIMER data showed that TLR10 expression was significantly positively correlated with immune infiltrates, especially infiltrating levels of B cells. Importantly, immunohistochemistry analysis revealed that TLR10 expression was a potential biomarker for distinguishing CNS-DLBC (also known as primary central nervous system lymphoma, PCNSL) from GBM. CONCLUSIONS Taken together, these results suggest that TLR10 could serve as a promising theranostic target for patients with glioma and is a potential biomarker for distinguishing PCNSL from GBM.