Nephrogenic systemic fibrosis (NSF) is a fibrosing disorder, recently described in patients with advanced chronic kidney disease, usually after exposure to gadolinium (Gd)-based contrast agents, characterized by progressive fibrotic involvement mainly of the skin. At clinical examination, the cutaneous findings of NSF may partly resemble those of systemic sclerosis. However, the different topographic distribution of the skin thickening and hardening, usually involving the limbs and trunk, whilst sparing the face, the lack of serologic abnormalities and the distinctive histopathological findings allow this new disease entity to be distinguished from systemic sclerosis and other scleroderma-like fibrosing disorders (scleromyxedema, scleredema, eosinophilic fasciitis, etc.). Herein, we describe what, to best of our knowledge, is the first, biopsy proven, Italian case of NSF, which highlights the issue of the differential diagnosis between NSF and scleroderma-like fibrosing disorders.