We report a case of Castleman's disease that developed tumor lysis syndrome spontaneously and after systemic chemotherapy. A 44-year-old male patient was admitted with a 2-week history of abdominal distension accompanied by dyspnea. Physical examination revealed multiple lymph node enlargements. After admission, spontaneous hemoperitoneum developed and he underwent exploratory laparotomy, with the removal of the ruptured spleen. Pathologic review of the splenic tissue and excised lymph node gave the diagnosis of multicentric Castleman's disease. He experienced two episodes of tumor lysis syndrome, initially spontaneous and then chemotherapy related, which needed vigorous management including hemodialysis and intensive fluid therapies. To our knowledge, this is the first reported case of Castleman's disease complicated by tumor lysis syndrome. This suggests that the possibility of tumor lysis syndrome should be considered when treating Castleman's disease with a large disease burden.