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Castleman disease (CD) is a rare lymphoproliferative disorder also known as angiofollicular lymph node hyperplasia or giant lymph node hyperplasia. CD can be unicentric CD (UCD) or multicentric CD (MCD). MCD affects more than one group of lymph nodes and/or lymphoid tissues and it is frequently associated with HIV and human herpes virus 8 (HHV-8) infections and, in contrast with UCD, it often results in systemic symptoms, such as fever, fatigue, anemia, inflammatory syndrome. HHV- 8-associated MCD recognizes HHV-8 as an etiopathogenetic agent and occurs generally in HIV-positive subjects. Our report describes an HHV-8 positive Castleman disease with plasmablastic microlymphoma occurring in a 51-year-old HIV seronegative woman, with a previous history of HBV infection and Kaposi’s sarcoma, who presented elevated procalcitonin levels during the acute phase of CD.