Tumefactive demyelinating lesion(TDL)is defined as a large lesion, size >2 cm, mass effect, perilesional edema and/or ring enhancement. TDL could occur in multiple sclerosis(MS), neuromyelitis optica spectrum disorder(NMOSD), acute disseminated encephalomyelitis(ADEM)or other immunological diseases. Non-invasive methods including MR imaging and assay of several autoantibodies(e.g. aquaporin-4 autoantibodies)are recommended when each TDL is identified. The radiological findings on MRI are characterized by size >2 cm, mass effect, perilesional edema, T2 weighted hypointense rim, peripheral diffusion restriction, open ring enhancement, vascular enhancement, and central vein sign. When atypical clinical and radiological presentations are present in patients with TDL, diagnosis may necessitate brain biopsy due to exclude alternative pathology(e.g. primary central nervous system lymphoma). Because treatments and outcomes for patients with TDL are dependent on each disease etiology including MS, NMOSD, ADEM or others, we should always clarify the entire picture behind the disease.