Des-gamma-carboxy prothrombin is an abnormal prothrombin which increases in the plasma of patients with hepatocellular carcinoma. To clarify the process of des-gamma-carboxy prothrombin synthesis, immunoreactive prothrombin, des-gamma-carboxy prothrombin, and vitamin K (phylloquinone and menaquinone) concentrations were determined in human liver tissue, including hepatocellular carcinoma. In the patients with elevated plasma des-gamma-carboxy prothrombin levels, both immunoreactive prothrombin and des-gamma-carboxy prothrombin significantly increased in hepatoma tissues compared with non-cancerous liver tissue. On the other hand, no significant difference was observed in the endogenous vitamin K (K1, MK-4, MK7) concentrations between hepatoma and noncancerous portions, in either the cases with or without increase of plasma des-gamma-carboxy prothrombin. These data strongly suggested that in the patients with an increase of plasma des-gamma-carboxy prothrombin, overproduction of prothrombin in hepatoma plays in important role in the synthesis of des-gamma-carboxy prothrombin.