Progressive multifocal leucoencephalopathy (PML) is an invariably lethal, progressive demyelinating disease, caused by the JC virus (the term consists of initials of the patient, in whom the virus has been first isolated – John Cunningham), of the Polyomaviridae family. Before, the JC virus was enumerated among the Papovaviridae, a family which includes also papillomaviruses. The JC virus has been isolated from brains of patients with progressive multifocal leucoencephalopathy and is considered the etiologic factor here, although it may also cause renal and upper respiratory tract diseases. Suggestions about viral aetiology of PML appeared as early as the ‘50s, but only ultrastructural studies by Gabrielle Zu Rhein revealed structures identical to virions of polyoma viruses. Microscopic lesions are usually much more pronounced than those visible by naked eye. Most often, these are symmetric, diffuse foci of subcortical demyelination, ranging from microscopic to large, confluent and encompassing most of the white matter in a particular area. Within these foci visible are oligodendrocytes featuring large basophilic nuclei with viral inclusion bodies and hypertrophic, monster astroglial cells.