Despite the various therapeutic strategies used in the treatment of acute febrile neutrophilic dermatoses, interferon-alpha has so far been proposed only as an intralesional monotherapy for cutaneous lesions and has only had partial success. We now describe the treatment of a long-standing, previously drug resistant, case of idiopathic Sweet's syndrome. After an initial successful combined short therapy with systemic interferon-alpha and hydroxyurea, the results were maintained by long-term treatment with interferon-alpha only. To our knowledge, this is the first report showing a clear response to the drug in a patient affected by Sweet's syndrome.