Vitamin B 12 , or B 12 , is an essential nutrient for humans, and its deficiency is a public health problem, especially in elderly population. Around 30% of circulating total B 12 levels are attached to transcobalamin II (TCN2), being referred as holotranscobalamin (holo-TC), and representing the biologically active fraction. After cellular uptake, B 12 participates in the homocysteine (Hcy) metabolism. The potential influence of the described TCN2 776C>G polymorphism upon B 12 intracellular delivery is a current target of research and we aimed to investigate its biochemical significance upon a healthy adult population.The TCN2 776C>G polymorphism was screened by PCR-RFLP in 122 individuals. Concentrations of plasma total B 12 , holo-TC, total Hcy and folate, as well as red blood cell folate, were determined.The studied polymorphism is common in the Portuguese population and significantly affects holo-TC but neither total B 12 nor total Hcy plasma concentrations, confirming that the TCN2 776C>G genotype exerts a significant influence upon B 12 cellular delivery.