With the aim to evaluate skin abnormalities in patients affected by amyotrophic lateral sclerosis (ALS) with respect to the dermal ultrastructure, including autonomic termination, microcirculation and sweat glands, 13 ALS patients and 5 controls underwent a skin biopsy of the left forearm. Abnormalities of the collagen and elastic fibrils were found in 4 and 5 patients respectively; amyelinic axons and sweat glands showed ultrastructural abnormalities in most ALS patients but not in controls; a quantitative evaluation of the collagen fibrils showed greater diameter of fibrils, larger interfibrillar spaces and more consistent size variation in ALS patients than in controls. These results suggest autonomic involvement in ALS and changes in the collagen fibril organization during the early stages of the disease.