Vitamin B12 (cobalamin) deficiency is a common disorder with potential irreversible haematological and neurological consequences. Currently used diagnostic tests such as the evaluation of serum vitamin B12 and the Schilling test are insufficient, e.g. the positive predictive value of a low serum vitamin B12 level for actual vitamin B12 deficiency (i.e. tissue deficiency) is low. Insufficient availability of vitamin B12 will lead to the accumulation of methylmalonic acid and homocysteine in the body. Nearly all patients with vitamin B12 deficiency also have substantially increased levels of methylmalonic acid and homocysteine. New tests of serum methylmalonic acid and homocysteine are highly sensitive for vitamin B12 deficiency and may obviate the need for the somewhat cumbersome Schilling test.