Our previous microarray analysis of gastric cancer found that claudin-4 was differentially expressed between intestinal-type gastric cancer (IGC) and diffuse-type gastric cancer (DGC). Claudin-4 is a member of a large family of transmembrane proteins, claudins, essential in the formation and maintenance of tight junctions. To explore the roles of claudin-4 in the two histologically distinct types of gastric cancer, we selected 45 IGC and 48 DGC cases and then analyzed the expression of the protein using immunohistochemistry. We found that the overexpression of claudin-4 was greater in IGC than in DGC. A trend was observed between the overexpression of claudin-4 and lymph node metastasis, however, this association was not statistically significant. The results showed that the expression of claudin-4 was lower in DGC. Possibly it played a role in determining the diffuse phenotype and loose cohesion of cells in DGC in a similar manner as E-cadherin.