Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare transmissible disease caused by accumulation of pathological prion protein in the CNS. sCJD typically affects patients in their sixties. The median disease duration in sCJD (6 months) is shorter than in variant Creutzfeldt-Jakob disease (vCJD) (14 months). The clinical diagnosis in sCJD is supported by the detection of periodic sharp and slow wave complexes (PSWC) in the electroencephalogram, 14-3-3 proteins in the cerebrospinal fluid (CSF) and hyperintense basal ganglia on magnetic resonance imaging (MRI). In contrast to sCJD, hyperintensities in the posterior pulvinar (the "pulvinar sign") are seen in vCJD. Different sCJD subtypes characterised by distinct neuropathological lesion profiles, clinical features and codon 129 genotype of the prion protein gene (PRNP) are described, together with the type with a proteinase K-resistant core of the prion protein. The sensitivity of diagnostic tests varies considerably in different sCJD subtypes. Alzheimer 's disease and Lewy body dementia are the most frequent differential diagnoses in elderly patients, while chronic inflammatory CNS disorders have to be considered in younger patients.