Primary small cell carcinoma of the esophagus (ESCC) is extremely rare. Twenty-two cases similar to the small cell carcinoma of the lung in histological features were diagnosed in this hospital during the past 30 years. Clinically, this tumor was highly malignant, rapidly growing and poor in prognosis. In our series, 18 of the 22 patients had died and 11 of them did so in about six months postoperatively. Histologically, 11 were of pure small cell type, 5 intermediate cell type and 6 combined small cell type. Neurosecretory granules were observed by electron microscopy in two cases. The results of immunohistochemical study with ABC method were as follow: EMA + 17/18, Keratin + 1/18, NSE + 9/18, S-100 protein + 1/18, but Chromogranin and Vimentin were negative. All the findings suggest that a small cell carcinoma of the esophagus may well be squamous, glandular, or neurosecretory differentiation, therefore supporting the opinion that this tumor is of total potential stem cell origin and that it may derive from the endoderm.