CD44, a family of cell surface glycoproteins involved in cell-cell and cell-extracellular matrix adhesion, is widely expressed in the white matter of the normal brain and in astrocytic gliomas under its standard form (CD44s also called CD44H). On the other hand, several variants have been found in brain metastases and rarely found in gliomas. We have investigated by immunohistochemistry CD44H and CD44v6 expression in 28 oligodendrogliomas. All tumors were CD44v6 negative whereas nearly all tumors were immunolabelled with anti-CD44H antibody. Immunostaining increased in parallel with grade and was particulary strong around vessels and in tumoral subpial nodules. Western blot analysis showed that oligodendrogliomas expressed the same 80-kDa CD44 isoform as normal brain. Since gliomas may arise from a dividing progenitor cell, we also studied CD44H expression during the oligodendrocyte lineage in vitro in parallel with specific markers of the O-2A cells. Precursor cells (PSA-NCAM positive), O-2A progenitor cells, as well as preoligodendrocytes (A2B5 positive cells) and immature oligodendrocytes (O4 positive cells), coexpressed CD44H. Our data showed that CD44H is expressed by cells of the oligodendrocyte lineage in vitro and by oligodendrogliomas in vivo especially in sites of dissemination such as subpial spaces. This suggests that CD44H could play a role in migration of tumor cells in oligodendrocytic tumors.