Prion diseases are histologically characterized by a spongiform encephalopathy. The early symptoms of Creutzfeldt-Jakob disease (CJD) and variant Creutzfeldt-Jakob disease (vCJD) are unspecific. To date, the definite diagnosis can only be made by histological examination of central nervous tissue, i.e. brain biopsy or post mortem. Therefore, diagnostic tests are being elaborated that suffice with cerebrospinal fluid or blood. Unlike the sporadic form of Creutzfeldt-Jakob disease, that involves the central nervous system exclusively, in the variant of the Creutzfeldt-Jakob disease the lymphoreticular system including the tonsils is involved, too. Hence, a tonsillar biopsy can be performed instead of a brain biopsy. In particular, the diagnostic criteria of both CJD and vCJD are described.