A growing body of data indicates the importance of ethnic and racial factors to many clinical and scientific considerations of cobalamin metabolism and its disorders. Blacks have significantly higher cobalamin and transcobalamin (especially transcobalamin II) levels than whites. Because serum cobalamin levels are often influenced by factors unrelated to cobalamin intake, stores, or deficiency, it is unclear whether the differences in levels reflect cobalamin status or not. The ethnic differences, which are present in cord blood, childhood, and pregnancy as well, probably arise from combinations of hereditary and acquired causes. It also appears that blacks have lower homocysteine levels than whites, metabolize homocysteine more efficiently, and do not show the same benefit from vitamin therapy. Modern surveys indicate that pernicious anemia is as common in blacks and, perhaps, Asian Indians as in whites. Moreover, the disease appears to be accelerated in blacks and, to a lesser extent, Latin Americans. Yet, for various reasons, such as the blunting or absence of hyperbilirubinemia and the frequent coexistence of microcytic disorders, cobalamin deficiency may be more difficult to recognize in blacks. Many of these observations of differences and new-found similarities raise important clinical and public health issues. Does the standard reference range for serum cobalamin, derived largely from white subjects, promote underrecognition of deficiency in blacks with their higher cobalamin levels? Or does it promote overdiagnosis of cobalamin deficiency in many whites with their lower levels? Given their lower rate of neural tube defects, possibly lower homocysteine levels, more efficient homocysteine metabolism and lesser impact of vitamin therapy on it, does the untargeted promotion of high folate intake provide less benefit to blacks than to whites while exposing them to an equal risk for adverse effects because of unrecognized pernicious anemia?