Plasmablastic lymphoma is an aggressive diffuse large B-cell lymphoma classically arising in the oral cavities and jaws of individuals infected with the human immunodeficiency virus (HIV). More recently, cases of plasmablastic lymphoma have been identified in individuals negative for HIV. We report a case of plasmablastic lymphoma presenting as a rapidly expanding upper extremity mass in a 66-year-old individual negative for HIV. Aggressive multiple-agent chemotherapy resulted in a dramatic improvement of all symptoms. Increasing awareness of plasmablastic lymphoma in individuals who are HIV negative can allow for a better understanding of its clinical course and for specific chemotherapeutic regimens to be developed.