Prion diseases are a group of neurodegenerative disorders of humans and animals that affect primarily the nervous system. They can be sporadic, transmitted by infection or familial. The hallmark of these diseases is the presence of microscopic vacuolization of the brain tissue, called spongiform degeneration, and of abnormal protein, called prion protein, which is a normal component of brain and other tissues. The abnormal prion protein is resistant to digestion with enzymes that breakdown normal proteins, and accumulates in the brain. Compared with classic form of CJD, variant CJD patients typically have illness onset at an unusually young age (median age 26 years versus approximately 68 years for classic CJD). The EEG in variant CJD patients is typically normal or shows non-specific abnormalities. A prominent, symmetrical pulvinar high signal on T2-weighted and/or proton-density--weighted MRI has been reported in most variant CJD patients. In variant CJD, but not other forms of CJD, there is prominent involvement of the lymphoreticular tissues. A tonsil biopsy with demonstration of a characteristic abnormal prion protein by western blot and immunohistochemistry can help establish a diagnosis of variant CJD.