Esophageal cancer is an aggressive disease with a generally poor prognosis. Frequently, patients present late with obstructive symptoms indicating advanced tumors. Therefore, serial histopathological investigations of esophageal cancer are now being performed more extensively, and several distinctive clinicopathological features have been demonstrated. In this review, we present some of the distinctive features of esophageal cancer and discuss their clinicopathological significance. These characteristics include: (1) the frequent presence of lymph node metastasis, (2) the morphological features and depth of tumor invasion, (3) the synchronous and metachronous occurrence of carcinoma of other organs, (4) the frequent coexistence of squamous epithelial dysplasia, (5) the frequent coexistence of intraepithelial spread, blood vessel, and lymphatic permeation, (6) the occasional existence of intramural metastasis, (7) the frequent coexistence of multiple primary carcinomas, and (8) the occasional coexistence of glandular differentiation with squamous cell carcinoma.