Background: The mucin components of the gastric gel layer function as a protective and lubricating factor against luminal acid and proteolytic enzymes. Alteration of mucin expression in gastric preneoplastic and neoplastic lesions has suggested potential roles in neoplastic processes. This study aimed to assess the clinicopathological and prognostic significance of MUC-2, MUC-4 and MUC-5AC in Japanese gastric cancer. Methods: Expression of MUC-2, -4 and -5AC was evaluated on tissue microarrays of gastric carcinomas and adjacent non-cancerous mucosa specimens by immunohistochemistry and compared with clinicopathological parameters and survival time of the patients. Results: The three mucins were found to be expressed to a lesser extent in gastric carcinomas in comparison with non-cancerous mucosa (p<0.05). MUC-2 expression was negatively correlated with tumor size, depth of invasion, and TNM staging of gastric cancer (p<0.05), while that of MUC-5AC was negatively associated with the depth of invasion, venous invasion, lymph node metastasis and TNM staging (p<0.05), but positively with MUC-4 and MUC-2 expression (p<0.05). There was higher MUC-2 expression in intestinal- than diffuse-type carcinomas (p<0.05). Kaplan-Meier analysis indicated no relationship between expression of the three mucins and the cumulative survival rate of patients, even stratified according to the depth of invasion (p>0.05). Conclusion: Down-regulated expression of MUC-2, -4 and -5AC may be involved in pathogenesis, invasion, metastasis or differentiation of gastric carcinoma. Their altered expression might therefore be employed as an indicator of pathobiological behavior.