A 55-year-old man was admitted to our hospital complaining of left hemiparesis. Magnetic resonance imaging (MRI) showed a smooth ring-like enhanced cystic tumor in the right parietal lobe. He underwent gross total resection of the tumor under neuronavigation and 5-aminolevulinic acid (5-ALA) fluorescence guiding method. Histopathological examination of the tumor showed small cells formed epithelioid solid nests with some focus of duct-like structure. On the basis of the MRI and operative and histological findings, this tumor was diagnosed as a metastatic poorly differentiated carcinoma, although the primary cancer could not be detected by metastatic work-ups. Afterward, this tumor recurred repeatedly. Histopathological examination of specimen from the fourth surgery indicated that the tumor was a glioblastoma (GBM). In the review of the histology and immunohistochemistry of the first tumor, atypical fibrillary cells were seen between solid nests and positive for glial fibrillary acidic protein, therefore the tumor was retrospectively diagnosed as epithelioid GBM. We assessed whether the changes in histopathology were accompanied by changes in the methylation status of O6-methylguanine methyltransferase (MGMT) promoter and the status of 5-ALA fluorescence. The methylation status of the MGMT promoter was found to have changed from methylated to unmethylated and 5-ALA fluorescence became positive along with the histological change.