The relationship between postoperative prognosis and plasma level of PIVKA-II (Protein induced by vitamin K absence or antagonist-II) was studied in 56 patients with hepatocellular carcinoma. The survival rate was significantly lower in patients with positive PIVKA-II when compared with that with negative PIVKA-II. Similar results were also obtained in cases with tumor not less than 6cm in diameter (group A, 43 cases). In accordance with these results, the frequency of intrahepatic metastasis or portal tumor thrombus was significantly increased in PIVKA-II positive cases and thereby the macroscopic stage became more advanced although no significant difference was observed in curability. Tumor diameter and frequency of massive type were also increased in PIVKA-II positive patients and all of eight cases with massive type were PIVKA-II positive. Furthermore, all patients with massive type had both intrahepatic metastasis and portal tumor thrombus and their prognosis was extremely poor when compared with that with nodular type, in whom the survival rate was not different between PIVKA-II positive and negative cases. Thus, the poor prognosis of PIVKA-II positive patients might be due to the increased frequency of massive type although the cause-effect relationship remains to be elucidated.