Functional defects in the CIP/KIP family of cyclin-dependent kinase inhibitors (CDKIs) have been shown to be associated with human malignancies. We immunohistochemically examined p57KIP2 (p57) expression in 92 patients with human esophageal squamous cell carcinoma (SCC) to determine the relationship between this expression and those of cyclin D1 and E. The p57 labeling index (LI) (defined as the percentage of p57-positive cells) in esophageal SCC was 43.3 +/- 3.2% (mean +/- standard error of the mean). In non-neoplastic esophageal epithelium, p57 staining was more frequently observed in the basal and parabasal cells than in surface layer cells. Immunostaining for cyclin D1 and E was observed in 28.2% (28/92) and 32.6% (30/92) of tumors, respectively. The median p57 LI in cyclin D1-positive cases was 66.2, and significantly higher than that in negative cases (31.9%) (p = 0.0009). There was no significant relationship between p57 LI and cyclin E expression (p = 0.147). As determined using Kaplan-Meier's method, loss of p57 immunoreactivity was not a prognostic factor for esophageal SCC (p = 0.548). Our in vivo findings suggested that p57 protein expression was positively correlated with cyclin D1 expression and that loss of p57 protein expression alone does not affect progression of esophageal SCC.