Small fiber neuropathy is a neuropathy that by definition affect the small (un)myelinated nerve fibers of the skin and their functions. Symptoms of the disease are especially burning neuropathic pain of the distal extremities as well as complaints of the autonomic nervous system, which can lead to considerable suffering of the patients. In this prospective cohort study, 100 patients with idiopathic SFN were systematically studied. The aim was to characterize the collective with regard to phenotypic differences. For this purpose, in addition to a detailed medical history, a clinical neurological examination, and a laboratory chemistry analysis, various additional instrumental diagnostics (QST, SudoscanTM, skin biopsy, electrophysiology) were performed. Especially the QST and the histopathological examination were informative in a large number of patients. Overall, the study population was examined with regard to possible phenotypic subgroups against the background of a common etiological background. Initially, the following groups were identified, among others: Presence of autonomic symptoms, distribution pattern of SFN, initial trigger of SFN, course of disease, and amplification or alleviation of SFN symptoms. Although SFN presents relatively homogeneously, interindividual differences appear to be too pronounced to form distinct, sharply delineated phenotypic subgroups with possible common etiologies. In addition to known acquired causes, possible risk factors of SFN were investigated by laboratory chemistry. A significant correlation between markers of oxidative stress (glutathione, vitamin C) and damage of (thinly) myelinated nerve fibers was found, so that oxidative stress could be a potential risk factor for SFN. Furthermore, a correlation between neurotoxic 1-deoxy-sphingolipid bases with nerve degeneration and dysfunction could be shown, so that an association with metabolic syndrome as a risk factor could be hypothesized. A further decisive finding was the inadequate care situation of SFN patients in most cases as well as a high level of suffering of the study participants.