Alpha-Fetoprotein (AFP) levels measured by RIA show a strong sensitivity for the biological diagnosis of malignant hepatoma (MH). However, this parameter lacks specificity. Previous observations of an alteration in vitamin B12 metabolism in the presence of hepatoma led us to study vitamin-B12-binding proteins. Vitamin B12, also called cobalamin, is transported in the blood by two proteins or transcobalamins: one is haptocorrin (HC), which is linked to most of the cobalamin, and the other is transcobalamin II, which is involved in tissue exchanges. In this work, the levels of AFP and transcobalamins were determined by RIA and radioisotope dilution assay, respectively. They were measured in patients with MH (group A) and in patients with other liver diseases (group B). Compared with group B, group A showed a significant increase in total serum HC (p less than 0.005). In conclusion, it was observed that MH is accompanied by increased levels of HC. The origin of these changes could be due to either an increase in HC synthesis or a catabolic defect.