ABSTRACT Background MSA is characterized by deposition of alpha‐synuclein (α‐Syn) in oligodendrocytes and central nervous system (CNS) neurons. After recently detecting phospho‐α‐Syn (p‐α‐Syn) in dermal nerve fibers of patients with Parkinson's disease (PD), we assessed skin biopsies from patients with MSA to evaluate its potential role as a biomarker. Methods Skin biopsies of patients with MSA (n = 12), idiopathic PD (n = 30), tauopathies (n = 15), and normal controls (n = 39) were analyzed. P‐α‐Syn within dermal nerves was detected by immunofluorescence staining. Results p‐α‐Syn was found in 67% of patients with MSA and Parkinson's disease, but not in patients with tauopathy or controls when analyzing 15 consecutive sections. Sensitivity could be increased to 75% and 73%, respectively, by analyzing serial sections. In contrast to PD, where p‐α‐Syn clustered in autonomic fibers, deposits were mainly found in unmyelinated somatosensory fibers in MSA. Conclusion α‐Syn pathology in MSA is not restricted to the CNS, and skin biopsy may be useful for the premortem study of p‐α‐Syn. © 2015 International Parkinson and Movement Disorder Society