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To give an overview of recent data on the use of skin biopsy as a diagnostic tool in neuropathies.The sensitivity and specificity of skin biopsy in detecting small fiber neuropathy is supported by new data. In many patients with small fiber neuropathy, a treatable disorder can be identified if a full workup is done. Skin innervation is affected in neuropathies formerly considered as the large fiber type, such as porphyria and chronic inflammatory demyelinating neuropathy. New methods have been devised to complement histological evaluation of skin innervation by in-vivo microscopy and by neurophysiological assessment of small nerve fibers. Skin biopsies have been used to learn more about the pathophysiology of neuropathies, such as the discovery of reduced vascular endothelial growth factor expression in diabetic neuropathy and the increase in cytokine expression in some painful small fiber neuropathies. Quantification of skin innervation has been used as a measure for treatment success in experimental studies and is presently used for follow-up in clinical trials.Skin biopsy in the diagnosis of neuropathy is moving from a method giving descriptive results to a tool that may be helpful in etiological diagnostics, as a follow-up in clinical trials, and in pathophysiological research.