Multicentric Castleman disease (MCD), or multicentric angiofollicular lymph node hyperplasia, is an idiopathic lymphoproliferative disorder that is only seldom reported in children. The clinical and laboratory findings that characterize this peculiar disorder are thought to result from increased interleukin (IL)-6 production. We report herein the case of a 13-year-old boy with a long history of hectic fevers and abdominal pain, accompanied by stunted growth and elevated biologic markers of inflammation. Surgical biopsies of a pancreatico-splenic mass and of mesenteric lymph nodes revealed mixed-type MCD, which was diagnosed 6 years after the first clinical symptoms appeared. He received combination chemotherapy (cyclophosphamide, vinblastine) associated with a monoclonal B-cell antibody (Rituximab). This treatment was well tolerated but ineffective. Given the reported success of IL-1 blocking agents for treating Still disease, another IL-6 linked disorder, we attempted to treat him with anakinra, an IL-1RA agonist. His overall state normalized and both his clinical and biologic signs dramatically improved. This is the first report of anakinra treatment for MCD. We conclude that anti-IL-1 blocking agents could be an interesting treatment alternative for MCD, a chronic debilitating disease, which still carries a poor prognosis.