CD98, which is identical to fusion regulatory protein-1 (FRP-1), has been reported to induce and regulate cell fusion and multinucleated giant cell formation. To investigate the association between CD98 and multinucleated giant cells (MNGCs) in glioblastomas, we investigate the CD98 immunoreactivity of MNGCs and the proliferative potential in CD98 immunoreactive MNGCs in paraffin-embedded sections obtained from patients with glioblastomas. Double immunohistochemical staining for CD98 and Ki67 as a mitotic marker were performed in formalin-fixed and paraffin-embedded specimens obtained from 16 patients with primary glioblastomas including MNGCs. Most CD98 immunoreactive (CD98+) tumor cells were negative for Ki67. CD98+ MNGCs were identified in 15 cases. CD98+ Ki67- MNGCs were identified in 14 cases and ranged in number from one to 48 (6.7 +/- 11.5). CD98- Ki67+ MNGCs were identified in 15 cases and ranged in number from one to 32 (11.1 +/- 9.6). Mitotic index (MI) of CD98+ MNGCs (4.8 +/- 2.7%) was significantly lower than that of CD98- MNGCs (91.1 +/- 24.6%) (P < 0001). These results suggest that multinucleated giant cell formation may be developed by fusion among CD98- producing cells in glioblastomas.