Background/Aims: Alpha-fetoprotein (AFP) mRNA-expressing cells are candidates for circulating tumor cells in hepatocellular carcinoma. We analyzed portal vein blood, peripheral blood, and peritoneal lavage samples to detect the presence of AFP mRNA-expressing cells, and explored their relationship with metastasis. Methods: We measured the AFP mRNA expression in 112 sets of portal vein and peripheral blood samples and 61 peritoneal lavage samples that had been obtained during surgery. We estimated the change in the positive ratio of patients with AFP mRNA, the associated background factors, and the rate of recurrence. Results: The change in AFP mRNA positivity in the peripheral blood specimens was remarkable, while that in the portal vein blood and peritoneal lavage samples was similar during hepatectomy. Tumor location was the only factor associated with AFP mRNA positivity. The rate of recurrence was higher in the patients who were positive for AFP mRNA than in those who were negative 9-24 months after hepatectomy. During this limited period, the recurrence rate in the AFP mRNA-positive cases was significantly higher than that in the AFP mRNA-negative cases (p = 0.0472). Postoperative AFP mRNA positivity was not related to very early recurrence (0-9 months) or multicentric liver carcinogenesis (>24 months). Conclusion: AFP mRNA positivity in the peripheral blood was elevated after hepatectomy, and the elevation depended on the tumor location. AFP mRNA positivity might contribute to recurrence-free survival 9-24 months after hepatectomy.