Glioma is the most common tumor in the central nervous system that portends a poor prognosis. Key genes negatively related to survival may provide targets for therapy to improve the outcome of glioma. Here, we report a protein-coding gene CLEC5A, which is the top 1 gene by univariate Cox regression analysis of 524 primary GBM samples. Expression of CLEC5A is significantly correlated with decreased overall survival in patients with glioma via large-scale analysis. An analysis of 2589 patient samples showed that CLEC5A expression is higher in (1) glioblastoma than in lower-grade glioma and nontumor tissue, (2) in the mesenchymal subtype than in other subtypes, and (3) in IDH1-wild type glioblastoma than in IDH1-mutated glioblastoma. Notably, this tumor-associated biomarker is expressed preferentially on myeloid cells over glioma cells. And it shows a strong co-expression with M2 macrophage biomarker. Furthermore, CLEC5A-associated genes are enriched in immunosuppressive biological processes. The silico flow cytometry also showed CLEC5A expression related to less tumor purity and more tumor-promoting leukocytes infiltration. In conclusion, we proposed a new M2 biomarker expressed on myeloid cells that may decrease survival in patients with glioma through immunosuppressive mechanisms.