Certain tumors of the esophagus that display both sarcomatous and carcinomatous features have long been recognized. The nomenclature, classification, and histogenesis remain controversial and the microscopic differential diagnosis from other esophageal malignancies can be challenging, particularly in small biopsies. In this paper, we review the literature of carcinosarcoma and present two cases of esophageal carcinosarcoma, describing their salient histologic, immunohistochemical, and ultrastructural features. Also, we assess the expression of MDM2 and CDK4 in the carcinomatous and sarcomatous compartments of our cases and we compare them with the expression of these oncogenes in selected cases of esophageal squamous cell carcinoma with prominent stromal reaction. In both of our cases, identification of some epithelial ultrastructural and immunohistochemical features in cells of otherwise sarcomatous phenotype lends support to the common epithelial origin of these neoplasms. Moreover, positive staining for MDM2 and CDK4 in our cases with equally strong reactions in both carcinomatous and sarcomatous elements provides evidence of a role for these molecules in the pathogenesis of carcinosarcoma. In contrast, in cases of squamous cell carcinoma with prominent stromal reaction only the epithelial cells stained strongly for MDM2 and CDK4. These differences in the MDM2 and CDK4 immunohistochemical profile between carcinosarcomas and carcinomas of the esophagus may assist in their differential diagnosis.