Giant cell glioblastoma (GCG) is one of a group of rare tumors in which the cell population is abnormally large and includes multinucleated cells of gigantic sizes. Immunohistochemical studies were performed on four GCG cases and found that all giant cells and/or tumor cells were positive for glial fibrillary acidic protein (GFAP), S-100 protein, and vimentin, thus verifying the tumor's glial origin. The nuclei of multinucleated giant cells of three adult cases were frequently immunostained for proteins expressed during the cell cycle (proliferating cell nuclear antigen (PCNA) and Ki-67), thereby demonstrating the proliferative capacity of these cells. By contrast, those of a 12 year old girl expressed these cell cycle markers rather infrequently. Alpha I-antitrypsin was detected with relatively high frequency in the giant cells, and its presence may explain their bizarre sizes and pericellular reticulin fiber formation. A literature review of 32 cases revealed that the GCG that occurs preferentially in young girls is a type of pleomorphic xanthoastrocytoma. By contrast, GCG in adult males has the same age incidence as ordinary glioblastomas and, as these, expresses high levels of cell cycle-related proteins. Thus, GCG, which is subclassified morphologically as ordinary glioblastoma, has distinct biological and clinical characteristics, with that in children requiring re-evaluation because of its similarities to pleomorphic xanthoastrocytoma.