The appearance of hepatocellular carcinoma (HCC) with contrast-enhanced ultrasound (CEUS) in the vascular phase is described and evaluated as to whether the enhancement pattern correlates with the degree of cellular differentiation. One hundred four HCCs were prospectively evaluated with CEUS using coherent-contrast imaging (CCI) and SonoVue with a low mechanical index (<0.2). The enhancement of HCCs in the vascular phase was analyzed according to the degree of pathological differentiation obtained by fine-needle biopsy. In the arterial phase, all HCCs except for four well differentiated ones (96.2%) showed enhancement ( P<0.05). Histological differentiation of hypoechoic lesions in the early portal phase (7 HCCs; 16%) significantly differed from hyperechoic (1 HCC; 1%) or isoechoic lesions (87 HCCs; 83.6%) ( P<0.05), with a significant probability of a worse differentiation in hypoechoic lesions. Histological differentiation of isoechoic lesions in the late phase (30 HCCs; 28.8%) significantly differed from hypoechoic lesions (74 HCCs; 71.2%) ( P<0.05), with a significant probability of a better differentiation in isoechoic lesions. CEUS using CCI and SonoVue revealed enhancement in the arterial phase in >95% of HCCs, with a few well-differentiated cases not being diagnosed due to the absence of enhancement. Echogenicity in the portal and late phases correlated with cellular differentiation.