OBJECTIVE To characterize enhancement patterns of focal hepatic lesions using C-cube gray scale sonography with a microbubble contrast agent and to evaluate its usefulness in differential diagnosis of hepatic lesions. METHODS Fifty-four patients with 58 focal hepatic lesions were examined with Levovist-enhanced C-cube gray scale sonography. The final diagnosis of hepatic lesions was 29 primary liver cancers, 4 metastases, 8 hemangiomas, 12 focal nodular hyperplasias, 2 inflammatory pseudotumors of the liver and 3 angiomyolipomas. The initiation time of enhancement in various lesions and enhancement duration after administration of contrast agent were compared. Vascular findings in lesions were classified as peripheral enhancement, homogenous enhancement, mosaic enhancement and no enhancement depending on microbubble signals in the lesion relative to the liver parenchyma. RESULTS The initiation time of enhancement in hemangioma (48+/-12 s) was significantly later compared to other lesions (P<0.05). The enhancement duration of malignancies (69+/-33 s in primary liver cancer, 61+/-23 s in metastasis) was significantly shorter compared to benign lesions (P<0.05). Intranodular enhancement appearing at arterial phase and decreasing at portal venous phase was considered characteristic for malignancy. Intranodular enhancement did not appear earlier than the liver parenchyma, and peripheral enhancement pattern was regarded as positive findings for hemangioma. Intranodular enhancement appeared in the arterial phase, and homogenous enhancement pattern sustained in the whole portal venous phase were regarded as positive findings for focal nodular hyperplasia. No microbubble signals appeared in two inflammatory pseudotumors of the liver. CONCLUSIONS C-cube gray scale sonography can demonstrate dynamic intranodular enhancement in various focal hepatic lesions. The information provided by this methodology may be useful in the differential diagnosis of hepatic lesions.