A 31-year-old man visited our hospital with a persistent cough. Computed tomography (CT) scans of his chest showed a very large mass and multiple nodular lesions in the right lung field, mediastinal and hilar lymph node enlargement and splenomegaly. Laboratory analysis showed polyclonal hyperimmunoglobulinemia and increased levels of serum C-reactive protein (14.05 mg/dl) and interleukin-6 (44.2 pg/ml). The pathological findings of lung specimens obtained using video-assisted thoracoscopy revealed hyperplasia of the lymphoid follicles with germinal centers, plasma cell infiltration which stained positively with either anti-κ chain or anti-λ chain antibodies, and fibrosis in the alveolar septum. We made a diagnosis of multicentric Castleman disease based on high levels of serum IL-6, multiple lymph node enlargement and splenomegaly, although this case had histological findings in common not only with Castleman disease but also with inflammatory myofibroblastic tumor. His abnormal chest radiography findings and laboratory data significantly improved 6 months after his first visit, without any treatment. Multicentric Castleman disease showing a very large mass is extremely rare.