Objective.—To evaluate the clinicopathologic features and the roles of p53 and MIB-1 in esophageal small cell carcinoma. Method.—Twenty patients (14 men and 6 women) with esophageal small cell carcinoma treated in our hospital from 1982 through 1996 were studied. The clinicopathologic features, treatment received, and survival data of these patients were documented. Representative tissue was collected from each tumor, and immunohistochemical preparations for p53 protein and MIB-1 were made. Results.—Small cell carcinoma accounted for 1.3% of all esophageal malignant tumors. The median age of patients at presentation was 60 years. On gross examination, the tumors were large ulcerative lesions (median length, 7.5 cm). In 17 patients in whom p53 immunohistochemical study was performed, p53 protein was detected in 65% (9 of 17). All stage IV tumors were negative for p53 expression. The median tumor cell MIB-1 score was high at 855 (range, 810–964) positive cells per 1000. Overall median survival was 3.4 months. In patients who underwent chemotherapy, there was significant response. Conclusions.—Esophageal small cell carcinoma is an aggressive tumor. Overexpression of p53 is associated with early stages of carcinogenesis. The high proliferative index, as defined by the MIB-1 immunohistochemical method, may be related to aggressive behavior and high sensitivity to chemotherapy and radiotherapy.