Guidelines on the use of skin biopsy in clinical practice have never described in detail how immunohistological staining process and microscopy analysis of skin samples should be performed. Although a consensus on these technical issues has been reached among highly referenced skin biopsy laboratories, a wide inter-laboratory variability in procedures still exists, conditioning skin biopsy diagnostic accuracy in a clinical setting and results heterogeneity in research.  To highlight in a simple way the most widely accepted procedures, Eleonora will step-by-step describe the staining process through bright field immunohistochemistry and indirect immunofluorescence with PGP 9.5 via pre-recorded video and short presentation. Through a light microscope with attached camera (or alternatively histological images video-library) she will give a practical demonstration of intraepidermal nerve fibers counting, providing useful tips to carry out a correct intraepidermal nerve fibre density calculation. She will then show how to approach a semiquantitative assessment of autonomic innervation of piloerector muscle and sweat gland stained by PGP 9.5 and specific autonomic markers, such as Dopamine-beta- hydroxylase and Vasoactive intestinal peptide. Some slides marked with alternative sensory biomarkers such as Growth associated protein 43 and TRPV1, nowadays principally used in a research setting, will also be shown, and discussed.