The transport of vitamin B_<12> (B_<12>) from food to cells depends on three B_<12>-binding proteins in mammals, haptcorrin (HC), intrinsic factor (IF), and transcobalamin II (TC II). The serum protein, TC II, transports B_<12> from the ileum to the tissue. The B_<12>-TC II complex (holoTC II) is then taken up into cells by receptor-mediated endocytosis. To date, at least 20 polymorphisms in the gene encoding TC II have been identified. Recently, the potential influence of TC II polymorphisms on serum holoTC II, serum B_<12>, methyl maronic acid (MMA), and total homocysteine (tHcy) status has been reported. This article summarizes the relationship between TC II polymorphisms and B_<12>-related markers, races, diseases, and structural changes in the protein.