Introduction Plasmablastic lymphoma is an aggressive non-Hodgkin lymphoma classically occurring in individuals infected with HIV. Plasmablastic lymphoma has a predilection for the oral cavity and jaw. However, recent case reports have shown lymphoma in the stomach, lung, nasal cavity, cervical lymph nodes and jejunum in HIV-negative individuals. We report what is, to the best of our knowledge, the first case of plasmablastic lymphoma occurring in the ano-rectal junction of an HIV-negative man. Case Presentation A previously healthy 59-year-old Caucasian man presented with painless rectal bleeding. Colonoscopy revealed a lesion in the ano-rectal junction, with pathological examination demonstrating atypical lymphoid cells consisting primarily of plasmablasts with rounded nuclei, coarse chromatin, small nucleoli and multiple mitotic figures. Immunohistochemical analysis showed the atypical cells were negative for CD45, CD20, CD79a and immunoglobulin light chains, but were strongly positive for CD138 and EBV-encoded RNA. The results were consistent with a diagnosis of plasmablastic lymphoma. Aggressive systemic chemotherapy and involved field radiation therapy resulted in complete clinical and pathological remission. Conclusion Increasing awareness of plasmablastic lymphoma in HIV-negative individuals and in this location is warranted.