Monofocal acute inflammatory demyelination (MAID), which is observable by CT and MRI as a well-enhanced mass lesion with prominent perifocal edema, is very similar to malignant gliomas radiologically, making differential diagnosis of the two pathologies difficult. The aim of this study was to assess the different metabolic activities between MAID and malignant gliomas by MRS, methionine-PET, choline-PET, and FDG-PET. Six patients with MAID underwent methionine, choline, and FDG-PET, and 4 of the patients also underwent magnetic resonance spectroscopy (MRS). The images obtained from these patients were compared with the corresponding images of 19 anaplastic astrocytomas (AA) and 21 glioblastomas (GBM). The mean choline/creatine ratio of MAID was significantly lower than that of GBM. There were no significant differences in the mean NAA/creatine and lactate/creatine ratios among these pathologies. The methionine T/N ratio of MAID was significantly lower than those of AA and GBM. The choline T/N ratio of MAID was significantly lower than that of GBM. There were no significant differences in the FDG T/N ratios among these pathologies. These results demonstrate that the metabolic activity of MAID significantly differs in part from that of malignant gliomas. Combined PET and MRS neuroimaging examinations may be useful for differential diagnosis of these pathologies.