To investigate the mitotic activity of multinucleated giant cells (MNGCs) with glial fibrillary acidic protein (GFAP) in glioblastomas, double immunohistochemical staining for GFAP and Ki67 was performed in formalin-fixed and paraffin-embedded specimens obtained from 12 primary glioblastomas with MNGCs including three giant cell glioblastomas. The Ki67 labeling index (LI:%) of GFAP+ tumor cells ranged from 0 to 5.6 (2.5+/-1.7, mean+/-standard deviation). The Ki67 LI of GFAP- tumor cells ranged from 18.6 to 35.9 (24.7+/-6.6). The Ki67 LI of GFAP+ cells was significantly lower than that of GFAP- cells (P<0.0001). The number of Ki67+ GFAP- MNGCs ranged from 0 to 23 (8.6+/-8.2). The number of Ki67- GFAP+ MNGCs ranged from 0 to 15 (6.2+/-5.1). There was no significant difference between them (P=0.42). The Ki67 LI of GFAP+ MNGCs was 10.4+/-12.6. The Ki67 LI of GFAP- MNGCs was 45.9+/-29.9. The Ki67 LI of GFAP+ MNGCs was significantly lower than that of GFAP- MNGCs (P<0.01). Our study suggested that MNGCs with mitotic capacity were not dominant and that GFAP+ MNGCs had little mitotic activity in glioblastomas. MNGCs identified in glioblastomas may develop via not only the proliferation of abnormal nuclei in a single tumor cell but also other processes.