PURPOSE: The transmembrane glycoprotein CD44 exists in a variety of isoforms generated by alternative splicing of the pre-mRNA. We studied the role of CD44-standard (CD44s) and CD44-variant6 (CD44v6) in gastric adenocarcinoma. MATERIALS AND METHODS: Immunohistochemical staining was performed in 101 patients with gastric adenocarcinoma who underwent radical gastrectomy at KGCC, Seoul Paik Hospital. The relationship of CD44s, CD44v6 expressions to the clinicopathologic parameters, p53 and Ki-67 were evaluated. RESULTS: CD44s and CD44-v6 expressions were found in 56.4% and 48.5%, respectively. CD44s expression was significantly correlated with lymph node metastasis, lymphatic invasion, and Borr mann type. CD44v6 expression was significantly correlated with sex, lymph node metastasis, lymphatic invasion, and perineural invasion and had a tendency toward p53 expression. In inte stinal type adenocarcinoma, CD44s expression had correlations with lymph node metastasis and CD44v6 had correlations with lymph node metastasis, lymphatic invasion. However, in diffuse type adenocarcinoma, CD44s and CD44v6 expressions had correlations with only Borrmann type. In multivariate analysis, lymph node metastasis was the most significant risk factor for CD44s and CD44v6 expressions in total cases and intestinal type adenocarcinoma. CONCLUSION: These data suggest that expression of CD44 v6 may play an important role in the regulation of lymph node metastasis in intestinal type adenocarcinoma of stomach.