Glioblastomas are associated with high mortality due to their aggressive growth and invasiveness. Interactions and functional cross-talk between tumor cells and their microenvironments are mediated by cell surface receptors that are responsible for cell-cell and cell-extracellular matrix adhesion. Central nervous tissues contain plenty of the glycosaminoglycan hyaluronan, and glioma cells express the major cell surface hyaluronan receptor, CD44. In this study, we analyzed the expression and roles of CD44 in human brain tissues. Normal brain tissues showed no or weak CD44 expression, while reactive astrocytes and astrocytoma cells expressed CD44 at variable levels. Immunohistochemically, a higher percentage and intensity of CD44-positive tumor cells were detected in high-grade astrocytomas compared with low-grade astrocytomas. Glioblastoma cells that express CD44 were localized in perivascular and perinecrotic lesions. The human glioma cell lines A172 and KG-1-C expressed CD44 mRNA and protein. Administration of monoclonal anti-human-CD44 antibody inhibited the migration of A172 cells, which are glioblastoma-derived, but did not affect cell growth. In conclusion, CD44 expression levels correlated with the histopathological grade of gliomas, and monoclonal anti-CD44 antibody inhibited the migration of glioblastoma cells. These findings suggest that CD44 is a potential therapeutic target of glioblastomas.