BACKGROUND: As human immunodeficiency virus (HIV)-infected individuals are living longer, non-AIDS-defining cancers are becoming increasingly recognized. Primary esophageal tumors in people living with HIV have seldom been reported. We sought to document patient, virologic, and tumor characteristics and clinical outcomes in this patient group. METHODS: International physicians involved in the care of AIDS-defining and non-AIDS-defining cancers accrued cases of primary esophageal malignant neoplasms in HIV-infected individuals. Patient demographics, HIV status, cancer risk factors, esophageal tumor characteristics, treatment, and outcomes were analyzed. RESULTS: A total of 19 patients with primary adenocarcinoma and/or squamous cell carcinoma of the esophagus were identified. The median age was 48 years (range, 35-69 years) and the median CD4 lymphocyte count measured 376 cells/microL (range, 42 to >1000 cells/microL) (to convert to x10(9)/L, multiply by 0.001). The majority of patients were men with a history of smoking or considerable alcohol consumption. Prior esophageal disease (reflux, peptic ulcers, and achalasia) was reported in almost half of all patients. Seven patients (37%) underwent surgical resection, 11 (58%) received fluorouracil-based chemotherapy, and 7 (37%) underwent radiotherapy; survival correlated with stage at cancer presentation. While the majority of patients died, only 5 deaths (26%) were attributed to progression of esophageal carcinoma. CONCLUSIONS: Primary esophageal carcinoma is another non-AIDS-defining cancer associated with moderate immunosuppression and lifestyle habits including tobacco and alcohol use. The biological behavior, treatment, and outcome of HIV-related esophageal cancer appear similar to the general population with this disease; the same screening and risk moderation strategies are likely to apply.