In the present study, the expression of cyclin D1, as detected by immunohistochemistry, was compared with other prognostic variables and its prognostic impact was evaluated in a group of 172 patients with squamous cell carcinoma (SCC) of the esophagus who underwent potentially curative resection therapy and in a second group of 38 patients with SCC of the esophagus who were treated by combined modality therapy (radiochemotherapy +/- surgery). Expression of cyclin D1 in surgically treated carcinomas correlated negatively with tumor differentiation (p = 0.026) but positively with mitotic activity (p = 0.0199) and nodal status (p = 0.040). There were no significant correlations with pT category. Patients with cyclin D1-positive carcinomas showed significantly worse overall survival than patients with cyclin D1-negative carcinomas, both in univariate (p = 0.0016) and in multivariate survival analyses (p = 0.0038). Expression of cyclin D1 in carcinomas with multimodal treatment was correlated with poor response to chemotherapy (p = 0.026) but not with overall survival. We thus consider expression of cyclin D1 to be an important parameter, predicting an unfavorable overall survival of surgically treated esophageal cancer patients.