Adenocarcinoma and squamous cell carcinoma account for the vast majority of esophageal malignancies. Other malignancies that can involve the esophagus include melanoma, sarcoma, and lymphoma. Gastrointestinal involvement with lymphoma has a variable incidence, as reported in the literature. However, primary involvement, as defined by Dawson, is extremely rare. Lymphoma has been linked to immunosuppressive conditions (such as AIDS), medications, and transplantation. We present what we believe to be the first case of primary esophageal lymphoma in a patient on long-term immunosuppression with azathioprine who was also infected with the hepatitis C virus (HCV). HCV has been postulated to have a relationship with B cell lymphomas.