Amphiregulin is an epidermal growth factor (EGF) which is a ligand of epidermal growth factor receptor (EGFR). Amphiregulin is the most enhanced EGFR ligand in colon cancer. Here we report on the expression of Amphiregulin using immunohistochemical staining in primary colorectal cancer, and the correlations between prognosis and various clinicopathological factors. We examined 174 consecutive patients who underwent curative resection of colorectal cancer, from January 2002 to December 2004. Amphiregulin was positive in 156 (90%) patients. Amphiregulin was found to be an independent predictor of overall survival [hazard ratio=6.25 (95% confidence interval=1.3-111.5; p=0.0144)] and relapse-free survival [hazard ratio=6.94 (95% confidence interval=1.5-123.2; p=0.0075)]. We conclude that the expression of Amphiregulin in a primary colorectal tumor is useful as an indicator of prognosis and as a predictor of recurrence.