The pathological hallmark in patients with painful neuropathies is a significant loss of intraepidermal nerve fibers. Alas, the simple count of intraepidermal nerve fibers does not explain why some, but not all, neuropathic patients develop neuropathic pain. It is, however, possible to perform much more detailed analysis of the skin biopsies. This talk will introduce new findings on detailed skin biopsy analysis related to neuropathic pain, with a special focus on neuronal and non-neuronal cells that may be important for neuropathic pain, including nociceptive glia cells such as Schwann cells, immune cells such as macrophages and Langerhans cells, mechanoreceptors (Merkel cells) and ion channels (NaV 1.7). Findings from these detailed histopathological signatures in humans will be correlated with signs and symptoms of carefully phenotyped patients with type 1 diabetes, diabetic polyneuropathy (DPN) without neuropathic pain and in patients with painful DPN. Lastly, results from a human model of small fiber neuropathy using prolonged 8% Capsaicin patch exposure and its influence on nerve fiber- and Schwann cell reinnervation will be presented. Our preliminary data indicate that Schwann cells and nociceptors are interdependent and that the reinnervation may correlate with phenotyping and sensory testing.