CD44, an integral membrane glycoprotein expressed by many cell types, serves as the principal transmembrane hyaluronate receptor and may be a determinant of metastatic and invasive behavior in carcinomas. This study was performed to investigate the relationship between CD44 splicing variants v4/5 and v6 expression and histopathologic prognostic factors (depth of tumor invasion, histologic classification, vascular and lymphatic invasion, and lymph node metastasis) in 107 gastric adenocarcinomas. In 107 cases of gastric carcinoma, the immunohistochemical stainining for CD44 v4/5 and CD44 v6 gave the following results. CD44 v4/5 was expressed in 40.2% and CD44 v6 in 67.3% of gastric carcinomas. The expression of CD44 v4/5 was correlated with histologic classification by Lauren (p<0.05), lymphatic invasion (p<0.05), and lymph node metastasis (p<0.004). In contrast, expression of CD44 v6 had no impact on prognostic markers. This study suggests the role of CD44 v4/5 in invasion, metastasis, and its prognostic significance in gastric adenocarcinoma.