Folate status has been shown to be inversely associated with colorectal cancer risk. Recently developed murine models of folate receptor, or folate binding protein (Folbp), deficiency indicate that Folbp1 is critical in folate homeostasis.These findings support the dual effect of folic acid supplementation on intestinal tumorigenesis observed in other chemical and genetic models of colorectal cancer.ApcMin/+Folbp1 +/- and ApcMin /+Folbp1+/+ mice were used to determine whether Folbp1+/- would increase intestinal tumorigenesis and whether this could be reversed by folic acid supplementation. We demonstrated that Folbp1+/- reduced blood and small intestinal mucosal folate concentrations at 2.5 months, which was reversed by folic acid supplementation, but did not affect blood folate concentrations at 4 months. The Folbp1 genotype did not modulate intestinal tumorigenesis in ApcMin/+ mice. However, folate status was inversely associated with proximal and mid small intestinal tumorigenesis, whereas Hcy was inversely associated with distal small intestinal and colonic tumorigenesis.