We report a Japanese case of human herpes virus-8 (HHV-8)-associated multicentric Castleman disease(MCD) complicated by hemophagocytic syndrome(HPS). A 60-year-old man presented with persistent fever and progressive pancytopenia in June 2004. On physical examination, anemia, icterus, hepatosplenomegaly, and generalized lymphadenopathy were detected. Laboratory findings showed elevated levels of serum ferritin and soluble interleukin-2 receptor. Anti-human immunodeficiency virus (HIV) antibody was negative. Bone marrow aspiration revealed a normocellular marrow with an increased number of hemophagocytic histiocytes. Biopsy of cervical lymph node disclosed pathological features compatible with the plasmablastic variant of Castleman disease. HHV-8 DNA was detected in the specimen from lymph node by polymerase chain reaction. Thus, the diagnosis of HHV-8-associated MCD complicated by HPS was made. The patient was treated with immunotherapy and subsequent chemotherapy. However, he died of bacterial sepsis after one-month therapy. This case report provides some evidence that HHV-8 may be a causative agent of MCD even in HIV-seronegative Japanese patients.