Lymphomatosis cerebri is considered a diffuse form of primary central nervous system lymphoma and very rare. It is not well recognized and may be misdiagnosed with infiltrating tumors, degenerative disorders, ischemic diseases, and infectious diseases developed in the brain. Awareness of the possibility of this rare disease and early biopsy are required for differential diagnosis and preventing poor clinical outcomes. We report a case with lymphomatosis cerebri who presented with rapid neurological deteriorations and review the relevant literatures.