We have demonstrated that folic acid inhibits cell proliferation and epidermal growth factor receptor (EGFR) activation in colon cancer cell lines. We examined the effect of one year supplemental folic acid (5 mg/day) on the rectal mucosal expression of β-catenin and pGSK3β, known to be affected by EGF-R, in patients with colorectal adenomas. Folic acid treatment significantly reduced nuclear expression of β-catenin (P<0.05) and cellular expression of pGSK3β (P<0.01) when compared to placebo. Folic acid may exert its chemopreventive effect, at least in part, through inhibition of nuclear translocation of β-catenin.