Multicentric Castleman’s disease (MCD) is a known entity with characteristics of lymphoproliferative syndrome, characterized by cytokine activation. Its association with human immunodeficiency virus (HIV) is frequently described, as well as its positivity for human herpesvirus 8 (HHV-8). However, some negative patients for the latter (called idiopathic MCD), may have an aggressive spectrum of the disease (characterized by the presence of cytopenia, renal failure, anasarca and organomegaly), known as TAFRO syndrome (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly). We present the case of a young patient recently diagnosed with HIV infection, in whom MCD was found, and with an aggressive course despite treatment, who met criteria for TAFRO syndrome despite HHV-8 positivity. J Med Cases. 2020;11(8):253-255 doi: https://doi.org/10.14740/jmc3523