Glioblastoma multiforme (GBM) accounts for approximately 12-15% of intracranial neoplasms. The GBM remains refractory to therapy because of tumor heterogeneity, local invasion, and non-uniform vascular permeability to drugs. Patients with GBM have the median survival of approximately 8-10 months, and for those cases where tumor recurs, the average time of tumor progression after therapy is only eight weeks. A combination of different treatment modes as surgery and chemo- or/and radiotherapy extend survival only for a short time, if any. Recently, tenascin-C (TN-C) as a dominant epitope in glioblastoma has been discovered. It is transiently expressed during organogenesis, absent or much reduced in most fully developed organs, but reappears under pathological conditions such as infection, inflammation, or tumorigenesis. It was found that the intensity of TN-C staining correlates with the tumor grade and that the strongest staining indicates poor prognosis.