The case of a primary esophageal carcinosarcoma, shown to express p53 protein, is presented. The patient, a 57-year-old male, presented with fever, weight loss, and clubbing, but without swallowing difficulties. A large intraesophageal tumor was found on radiologic imaging, and sarcoma was diagnosed on esophagoscopic biopsy. Despite total esophagectomy and adjuvant chemo-radiotherapy, pleural metastases developed 3 months postoperatively. Histologically, the tumor was composed of epithelial and sarcomatous elements. Using monoclonal and polyclonal anti-p53 antibodies, p53 protein was distributed heterogenously throughout the sarcomatous elements of the primary tumor. Immunoreactivity was also found in regional lymph node metastases. These observations further implicate the p53 tumor suppressor gene in the pathogenesis of human esophageal cancers.