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The coexistence of systemic sclerosis (SSc) and multiple sclerosis (MS) in the same patient has been described in few cases. We refer here a further case of association between these diseases, which highlight the difficulty of treating such patients. A 57-year-old male with relapsing-remitting MS since 20 years, shortly after having received high-dose corticosteroids for a relapse of MS, suddenly developed SSc, with onset of Raynaud phenomenon simultaneous to that of scleroderma skin involvement, new appearance of accelerated arterial hypertension, and rapidly progressive oliguric renal failure, indicative of scleroderma renal crisis, that was controlled with ramipril, irbesartan and amlodipin. A further disabling relapse of MS was treated with interferon-beta, but 19 months later he developed multiple severe digital necrotic ulcers, that resolved with interferon discontinuation and therapy with iloprost. This case report shows that some form of treatment useful for MS might enhance the manifestations of SSc. [ABSTRACT FROM AUTHOR]