The bcl-2 proto-oncogene is a known inhibitor of apoptosis and may be an important regulator of tumor growth. In the present study, bcl-2-protein expression was investigated by immunohistochemistry and correlated with prognosis in a series of 150 potentially curatively resected squamous-cell carcinomas of the esophagus. For comparison, bcl-2-protein expression was analyzed in normal esophageal mucosa, severe squamous dysplasias and carcinomas in situ. bcl-2 immunoreactivity was found in 40 out of 150 invasive squamous-cell carcinomas; the remaining carcinomas were completely negative. bcl-2-protein expression was found more frequently among poorly differentiated than among well-differentiated tumors (p < 0.0001). No correlation was found between bcl-2-protein expression and the parameters tumor size, depth of invasion and nodal status. Moreover, bcl-2-protein expression had no significant influence on overall survival. Whereas in normal mucosa bcl-2 immunoreactivity was restricted to the basal-cell layer, in 9 out of 15 severe squamous dysplasias and in 7 out of 14 carcinomas in situ bcl-2 staining was detected in all epithelial layers. Thus, bcl-2-protein is frequently expressed in invasive squamous-cell carcinomas of the esophagus and in precursor lesions of esophageal cancer, but has no significant impact on the outcome of esophageal cancer.