PURPOSE: The CD44 is a cell surface adhesion molecule that plays a role in lymphocyte homing, cell migration, and cancer metastasis. It has been reported that the expression of CD44v6, which is one of the CD44 variants, is related to tumor progression, recurrence and metastasis in colorectal cancer This study examined the relationship between CD44v6 over-expression and the depth of invasion, lymph node metastasis, and evaluated the clinical significance of CD44v6 as a prognostic factor of colorectal cancer. METHODS: Immunohistochemical staining of CD44v6 was performed on 72 patients who underwent radical surgery for colorectal cancer. Positive expression of more than half of the carcinoma cells was regarded as `over-expression', and that of less than half was regarded as being `low-expression'. The degree of CD44v6 expression according to depth of the invasion and lymph node metastasis was analyzed, and the 5-year survival rate of the patients was calculated. RESULTS: CD44v6 over expression was identified in 22 cases (30.6%). There was a significant correlation between CD44v6 over-expression and a lymph node metastasis, but not between CD44v6 over-expression and the depth of invasion. In addition, the 5-year survival rate was lower in the CD44v6 over expression cases (31.8%) than in the low-expression cases (90.0%)(P<0.001) Multivariate analysis, CD44v6 was regarded as a significant prognostic factor for survival in colorectal cancer patients. CONCLUSION: These results suggested that CD44v6 over- expression might be a useful prognostic indicator in colorectal cancer.