Creutzfeldt-Jakob disease (CJD) is a rare, fatal neurodegenerative disease caused by an infectious protein called prion and is characterized by spongiform changes, neuronal loss, reactive astrocytic proliferation and accumulation of pathologic cellular protein, occurring in 3 general forms: sporadic or spontaneous, genetic or familial, and acquired form including a variant form of CJD. Clinical presentation of CJD is characterized by progressive dementia, neurologic symptoms and visual impairment, development of akinetic mutism, and eventually death, usually from respiratory infection. The diagnosis is based on clinical presentation, electroencephalogram, and typical cerebrospinal fluid and magnetic resonance imaging findings. A case is presented of a 56-year-old woman with progressive dementia, typical neurologic symptoms, positive cerebrospinal fluid and typical magnetic resonance imaging findings. The clinical, pathologic and imaging findings of this rare condition are also discussed.