In the diagnosis of diseases of the central and peripheral nervous systems, the use of electron microscopic analyses has become rare these days. However, there are questions in which the method is helpful in confirming the etiopathogenesis of the disease. Hereditary neurodegenerative and metabolic diseases, such as the lysosomal storage disease neuronal ceroid lipofuscinosis, are associated with pathognomonic storage products not only in the central nervous system (CNS) but also in extracerebral tissues such as sweat glands and lymphocytes. These tissues are easily accessible and thus function as "windows to the CNS". In addition, there are new methods that overcome limitations of conventional electron microscopy and may improve ultrastructural diagnostics. This is particularly important for the correct classification of viral particles such as SARS-CoV‑2, leading to a better understanding of COVID19-associated diseases in the CNS and peripheral nervous system.