The aim of this study is to describe the clinical characteristics and outcome of multicentric Castleman disease (MCD) in HIV-infected patients at an oncological referral center in Mexico. Clinical records at the HIV-AIDS clinic of all patients diagnosed with MCD from 1994 to 2018 were reviewed. There were 19 patients, mean age was 31.3 ± 8.4 years, and 17 (89.5%) were males. Fifteen patients (79%) had also Kaposi sarcoma (KS). Main clinical characteristics were multiple lymphadenopathy (95%), systemic symptoms (63%), and hepatosplenomegaly (50%). Computed tomography scan and 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography showed multiple lymphadenopathy, inversion of the liver:spleen uptake ratio, with an increase in SUVmax (5.7). The histopathology report described plasma cells in 58%, mixed type in 26%, and hyaline vascular in 16%. Eleven patients (57.9%) received different chemotherapy regimens. Seven patients died (36.8%): four related to MCD progression or chemotherapy complications, median survival was eight months. For those patients who survived, median, follow-up was 28 months (p < 0.001). The incidence of MCD in people living with HIV is probably underestimated. In patients with lymphadenopathy, B symptoms, deranged inflammatory markers, and/or disseminated KS, a biopsy of an enlarged lymph node is warranted, and the histology should be reviewed by an experienced pathologist.