Tumefactive demyelination is sometimes difficult differentiate from malignant tumors. Positron emission tomography with C-11-methionine is useful for diagnosing cerebral malignant tumors, but there are previous reports for tumefactive demyelination. We experienced a 32-year-old man who suffered from subacute onset dysarthria and left hemiparesis with magnetic resonance image of a large lesion (5.3 x 4.2 cm) in the right frontal lobe. Positron emission tomography with F-18-fluorodeoxyglucose showed a high ring-shaped glucose uptake in the lesion and C-11-methionine showed a remarkable methionine uptake in the whole lesion. Although a malignant tumor was suspected, the patient was finally diagnosed with tumefactive demyelinating disease based on brain biopsy results, and was treated completely by methylpredonisolone therapy. Although C-11-methionine uptake with positron emission tomography commonly suggests a malignant tumor, there can still be a possibility of tumefactive demyelinating disease.