We investigated correlations between laboratory test results and multicentric development of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) in 202 patients who underwent liver resection. Two types of HCC were considered to meet multicentricity criteria: in one, at least one tumor was well-differentiated, with at least one other being less differentiated; in the other, all tumors included well-differentiated HCC with or without less differentiated components. Forty-five patients had multicentric HCC. Platelet counts were lower in patients with multicentric HCC than in others. Serum concentrations of type IV collagen 7s domain and alpha-fetoprotein, histologic hepatitis activity score, and histologic hepatic fibrosis score were higher in patients with multicentric HCC. By multiple logistic regression analysis, low platelet count was an independent risk factor for multicentric HCC. The proportion of patients with multicentric HCC was significantly higher among patients with low platelet counts (below 10(5)/mm(3)) than in patients with a higher count. Thus, HCC patients with a platelet count below 10(5)/mm(3) may require particularly careful examination for multicentricity.