Background: Tenascin-C is an extracellular matrix protein known to correlate with prognosis in patients with glioblastoma, probably by stimulation of invasion and neoangiogenesis. Transforming Growth Factor-beta 1 (TGF-beta 1) plays an important role in the biology of high-grade gliomas, partly by regulating Invasion of these tumors into parenchyma. This study was designed to evaluate if TGF-beta 1 induces the expression and deposition of Tenascin-C in the extracellular matrix of high-grade gliomas which may be pivotal for the invasion of these tumors into healthy parenchyma. Methods: A series of 20 high-grade gliomas was stained immunohistochemically with Tenascin-C- and TGF-beta 1-specific antibodies. Expression levels of both proteins were evaluated and correlated with each other, time to progression and molecular and morphological markers of invasion. A quantitative PCR assay was performed evaluating the induction of Tenascin-C mRNA by treatment with TGF-beta 1 in vitro. Results: Tenascin-C was expressed in 18 of 19 (95%) evaluable tumors, whereas 14 of 20 tumors (70%) expressed TGF-beta 1 in a significant percentage of cells. Treatment with TGF-beta 1 did induce the expression of Tenascin-C at the mRNA and protein level in vitro. The expression of Tenascin-C and TGF-beta 1 did neighter statistically correlate with each other nor with time to progression. Conclusion: In our series, Tenascin-C and TGF-beta 1 were expressed in the vast majority of high-grade gliomas. We could not detect a correlation of one of the proteins with time to progression. Nevertheless, we describe induction of Tenascin-C by TGF-beta 1, possibly providing a mechanism for the invasion of high-grade gliomas into healthy parenchyma.