The most widely distributed form of transmissible spongiform encephalopathy, sporadic Creutzfeldt-Jakob disease, typically affects patients in their sixties. Rapidly progressive dementia is usually followed by focal neurological signs and typically myoclonus. The disease duration in sporadic CJD is shorter than in variant CJD (6 months and 14 months, respectively). The clinical diagnosis in sporadic CJD is supported by the detection of periodic sharp and slow wave complexes in the electroencephalogram, hyperintense signals in basal ganglia on magnetic resonance imaging and elevated levels of neuronal proteins in the cerebrospinal fluid (such as 14-3-3). In contrast to the sporadic form, hyperintense signals in the posterior thalamus ("pulvinar sign") are seen in variant CJD. Following recent developments in diagnostic premortem techniques, clinical criteria for probable sporadic and probable variant CJD were established. Clinicopathological studies on sporadic CJD revealed different phenotypes which are characterized by neuropathological lesion profile, clinical syndrome, codon 129 genotype and type of proteinase K-resistant core of the prion protein. Alzheimer's disease and Lewy body dementia are the most frequent differential diagnoses in sporadic CJD in elderly patients, whereas chronic inflammatory disorders of the central nervous system have to be considered in younger patients.