Thrombocytopenia (T), anasarca (A), myelofibrosis (F), renal dysfunction (R), and organomegaly (O) (TAFRO) syndrome is a variant of multicentric Castleman's disease. We describe here a 57-year-old man who presented with persistent fever, pleural effusion, and ascites. He was negative for human immunodeficiency virus and human herpes virus-8. A computed tomography scan showed an anterior mediastinal mass and small inguinal lymphadenopathy. Although a biopsy of the anterior mediastinum showed fatty tissue infiltrated with CD20(+) and CD45RO(+) lymphocytes, a biopsy of the left inguinal lymph node revealed a hyaline vascular type of Castleman's disease. He subsequently developed severe thrombocytopenia and renal dysfunction. In addition, his bone marrow biopsy showed myelofibrosis. TAFRO syndrome was diagnosed based on the lymph node pathology and the characteristic manifestations of the syndrome. Tocilizumab and glucocorticoid therapy achieved complete remission and regression of the mediastinal mass. To our knowledge, this is the first report of TAFRO syndrome accompanied by an anterior mediastinal mass, which responded very well to therapy.