AIMS: To assess whether standard and variant isoforms of CD44 (CD44s, CD44v5, and CD44v6) have a differential expression profile in early versus advanced gastric adenocarcinoma of the diffuse and intestinal types and their metastases. METHODS: Immunohistochemical expression of CD44s, CD44v5, and CD44v6 was evaluated in 14 early gastric cancers (nine intestinal and five diffuse) and 37 advanced adenocarcinomas (21 intestinal and 16 diffuse) as well as in 18 cases of perigastric lymph node metastasis. Ten normal and five metaplastic gastric mucosa samples were also included in the study. RESULTS: Although no significant association was found between the degree of invasion and the CD44 expression profile, CD44v6 positivity was detected more frequently in metastases of intestinal-type carcinomas (66%) than in metastases of diffuse-type neoplasms (11%) (p < 0.05). Weak CD44s, CD44v5, and CD44v6 expression was observed focally in both normal and metaplastic gastric mucosa samples. CONCLUSIONS: These data suggest that CD44v6 expression may be involved in the production of lymph node metastases in intestinal-type gastric carcinoma but not in the diffuse-type disease, the metastatic potential of which is most likely unrelated to the CD44 family of adhesion molecules.