Mucoepidermoid carcinoma of the esophagus is a particularly rare lesion, and only 24 cases have been reported in the English literature. Using histochemical methods, we identified four (3.1%) of 135 resected primary esophageal cancers as mucoepidermoid carcinomas. Gross examination of these four tumors disclosed sclerosing submucosal infiltration with shallow surface ulceration, which had appeared as a funnel-shaped constriction on esophagram. The intraepithelial spread of the tumor in two cases and the close relationship between foci of invading carcinoma and regions of dysplastic epithelium in the remaining two cases suggest that esophageal mucoepidermoid carcinoma may originate in the squamous epithelium. Although mucoepidermoid carcinoma should theoretically offer a fair prognosis, the outcome for patients with this lesion has generally been as poor as patients with typical squamous cell carcinoma. This further implies that mucoepidermoid carcinomas may arise from the squamous epithelium.