Aims. Epstein-Barr virus (EBV) is causally associated with many hematolymphoid malignancies. This laboratory-based study aimed to establish the prevalence of EBV in plasma cell neoplasms in a large South African cohort and to determine whether there is any correlation between EBV-positivity and human immunodeficiency virus (HIV) status in patients with plasma cell neoplasms, including plasma cell myeloma and plasmacytoma (solitary plasmacytoma of bone and extraosseous plasmacytoma). Methods. This single-institution retrospective study included all patients with a histopathologic diagnosis of plasma cell neoplasm between 2003 and 2020. EBV-expression in the plasma cell neoplasms was assessed by EBV-encoded RNA (EBER) in situ hybridization (ISH) and correlated with HIV status. HIV status was determined by retrieving prior serologic results. Formalin-fixed paraffin-embedded tissue from HIV-unknown patients underwent HIV-1 p24 antibody testing. Results. Sixteen of 89 plasma cell neoplasms (18%) were EBV-positive. There was a significant correlation between EBV and HIV infection in plasma cell neoplasms, with 6/10 tumors from HIV positive patients showing EBV-positivity in tumor cells. The EBV-positive cohort was significantly younger than the EBV-negative group. Conclusion. EBV-positivity in plasma cell neoplasms in this study is higher than previously reported. The significant occurrence of EBV in plasma cell neoplasms from HIV-positive patients suggests a co-carcinogenic relationship between the two viruses.