Changes in the plasma concentration of malignant disease-associated DNA-binding protein 2 (MAD2) and in the distribution of fibronectin and MAD2 in liver tissue were studied in Fisher-344 rats with diethylnitrosamine-induced hepatocarcinogenesis. The concentration of plasma MAD2 significantly increased as pre-cancerous lesions developed into hepatocellular carcinoma. We believe that the increased plasma concentration of MAD2 is caused by an increase in the degradation of fibronectin within hepatocellular carcinoma tumors. Therefore MAD2 may be a useful marker for the early detection of hepatocellular carcinoma.