Caveolin-1 (CAV1) and caveolin-2 (CAV2) are the major structural proteins of caveolae. We investigated the relationship between the clinicopathological factors of esophageal squamous cell carcinoma (ESCC) and the expression of CAV1 and CAV2. CAV1 and CAV2 expression were analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 15 esophageal cancer cell lines (TE1-15) and a normal esophageal epithelium cell line (Het-1A). CAV1 and CAV2 expression was examined by RT-PCR and immunohistochemical analysis in 47 ESCC specimens. High levels of CAV1 and CAV2 mRNA were detected in TE1-15, but neither CAV1 nor CAV2 mRNA were detected in Het-1A. In the ESCC samples CAV1 and CAV2 mRNA expression in the ESCC samples were significantly higher than in the corresponding normal esophageal mucosa (CAV1, P=0.0024; CAV2, P=0.0136). However, we could not find any significant relationship between CAV1 or CAV2 mRNA expression and clinicopathological factors. Immunostaining for CAV1 was positive in 13 of 47 patients (27.7%), whereas CAV2 was positive in 22 of 47 patients (46.8%). A significant correlation was observed between CAV1 and CAV2 immunostaining and T factor, lymphatic invasion, vein invasion and differentiation. The patients with positive staining for CAV1 or CAV2 had a significantly shorter survival than those with negative staining (P=0.0105 and 0.0424 for CAV1 and CAV2, respectively). These results suggest that positive staining for CAV1 and CAV2 could be a potentially useful prognostic marker of ESCC.