Background. It is often difficult to differentiate Parkinson's disease (PD) from multiple system atrophy (MSA), especially in their early stages. Objectives. To examine the clinical utility of histopathological analysis of biopsied skin from the chest wall and/or leg in differentiating between the two diseases. Methods. Skin biopsies from the lower leg and/or anterior chest wall were obtained from 38 patients with idiopathic PD (26 treated with levodopa and 12 levodopa-naïve) and 13 age-matched patients with MSA. We sought aggregates of phosphorylated α-synuclein on cutaneous nerve fibers using double fluorescence immunohistochemistry and confocal microscopy and measured intraepidermal nerve fiber density (IENFD). Results. Phosphorylated α-synuclein aggregates were identified on cutaneous nerves in two patients with PD (5.3%) but in none of the patients with MSA, and IENFD was significantly lower in patients with PD when compared to those with MSA. There was no difference in IENFD between levodopa-treated and levodopa-naïve patients with PD. Conclusions. Our findings suggest that an assessment of IENFD in biopsied skin could be a useful means of differentiating between PD and MSA but that detection of α-synuclein aggregates on cutaneous nerves in the distal sites of the body is insufficiently sensitive.