C-kit is a proto-oncogene involved in normal growth and development and neoplastic processes, and its product, CD117, is a highly specific immunohistochemical diagnostic marker for gastrointestinal stromal tumors (GISTs). Because GISTs that express immunohistochemically-detectable CD117 respond dramatically to treatment with tyrosine kinase inhibitors, identification of central nervous system tumors that express CD117 might open new therapeutic approaches for treatment of brain tumors. Specimens from 52 glial tumors of various histologic types and grades were assayed for CD117 immunoreactivity, and about 75% of the tumors were positive for CD117 expression; all except a few exhibited strong cytoplasmic and membranous staining. The proportion of high grade tumors of all tumor types with detectable CD117 immunoreactivity was statistically significantly greater than low grade tumors, and glioblastoma and anaplastic oligodendroglioma showed the highest staining grade. These findings support further investigation into the possibility that CD117 has an important role in growth of glial tumors and that patients with brain tumors expressing CD117 might benefit from treatment with receptor tyrosine kinase inhibitors.