Plasmablastic lymphoma (PBL) of the oral cavity is an acquired immunodeficiency syndrome-related lymphoma. The immunophenotype of this disease is associated with poor expression of B-cell markers but a positive reactivity for plasma cell markers. PBL is highly aggressive and responds poorly to treatment. Although originally described in the oral cavity, this disease can occur in other body niches. Here, we describe a very rare case of PBL in the anal canal of a 40-year-old woman with human immunodeficiency virus infection. The malignant cells were positive for Epstein-Barr virus and human herpes virus 8.