It has been demonstrated that CD34-positive cells isolated from human peripheral blood differentiate into endothelial cells and contribute to neoangiogenesis in adults. We investigated the role of CD34-positive endothelial cells in liver samples from patients with hepatitis B virus (HBV)-associated chronic liver diseases. Tissue sections were obtained by liver biopsy from 25 patients with HBV-associated chronic liver diseases and were examined by immunohistochemistry using anti-CD34, anti-von Willebrand factor (vWF), and anti-vascular endothelial growth factor (VEGF) antibodies. CD34-positive, but vWF-negative endothelial cells were observed, particularly in the sinusoids and vascular endothelial cells. We counted these cells and expressed the results as a CD34-labeling index (LI). The CD34 LI did not correlate with VEGF expression and the CD34 LI of patients who progressed to hepatocellular carcinoma (HCC) tended to increase compared to those that did not progress to HCC. CD34 LI was an independent risk factor for development of HCC (relative risk, 35.689; P = 0.033). We conclude that CD34-positive endothelial cells in patients with HBV-associated chronic liver diseases might play a role in hepatocarcinogenesis.