We report a case of severe Churg-Strauss syndrome (CSS) with mediastinal eosinophilic lymphadenopathy, with relapse after standard therapy with steroids and cyclophosphamide, subsequently treated with interferon (IFN) alpha 2b. Our report shows that mediastinal lymph nodes mimicking lymphoma may be one of the clinical manifestations of CSS. We also show that patients with CSS who are resistant to first-line therapy and for whom hypereosinophilia is thought to play an important role may benefit from treatment with IFN.