Background Plasmablastic lymphoma (PBL) is an uncommon type of B-cell–derived lymphoma that displays distinctive affinity for extranodal presentation in the oral cavity. PBL is strongly associated with human immunodeficiency virus (HIV) infection, but has been reported in HIV-negative individuals. PBL pursues an aggressive clinical course and the prognosis is poor, despite therapy. Plasmablastic lymphoma can be the presenting finding in a previously undiagnosed HIV-positive patient. Study design Five cases of oral cavity lymphomas conforming to the current WHO morphologic criteria for PBL were retrieved from the consultation files at AFIP. An immunohistochemical panel consisting of CD3, CD20, CD30, CD38, CD45RB (LCA), CD79a, CD138, Bcl-2, Bcl-6, Alk-1, Ki-67, and LMP-EBV was performed. Clinical follow-up, including HIV status, was pursued for each case. Results Morphologically, sheets of large immunoblast-like cells with a high mitotic rate characterize PBL. The nuclei are eccentrically placed with a single prominent nucleolus. The abundant cytoplasm is deeply basophilic with a paranuclear hof. Scattered tingible body macrophages and necrosis are present as well. PBL is immunoreactive with CD38, CD138, and CD79a but shows minimal or absent expression of CD45RB (LCA) as well as CD20. Follow-up information was also pursued. Conclusion Recognition of this distinctive type of lymphoma, confined mostly to the oral cavity, is important to avoid confusion with other malignancies. Plasmablastic lymphoma (PBL) is an uncommon type of B-cell–derived lymphoma that displays distinctive affinity for extranodal presentation in the oral cavity. PBL is strongly associated with human immunodeficiency virus (HIV) infection, but has been reported in HIV-negative individuals. PBL pursues an aggressive clinical course and the prognosis is poor, despite therapy. Plasmablastic lymphoma can be the presenting finding in a previously undiagnosed HIV-positive patient. Five cases of oral cavity lymphomas conforming to the current WHO morphologic criteria for PBL were retrieved from the consultation files at AFIP. An immunohistochemical panel consisting of CD3, CD20, CD30, CD38, CD45RB (LCA), CD79a, CD138, Bcl-2, Bcl-6, Alk-1, Ki-67, and LMP-EBV was performed. Clinical follow-up, including HIV status, was pursued for each case. Morphologically, sheets of large immunoblast-like cells with a high mitotic rate characterize PBL. The nuclei are eccentrically placed with a single prominent nucleolus. The abundant cytoplasm is deeply basophilic with a paranuclear hof. Scattered tingible body macrophages and necrosis are present as well. PBL is immunoreactive with CD38, CD138, and CD79a but shows minimal or absent expression of CD45RB (LCA) as well as CD20. Follow-up information was also pursued. Recognition of this distinctive type of lymphoma, confined mostly to the oral cavity, is important to avoid confusion with other malignancies.