To characterize focal liver lesions (FLLs) using real-time contrast-enhancedsonography (CEUS) with a low mechanical index mode and a sulfur hexafluoride-filled microbubble contrast agent. CEUS was performed in 190 patients with FLLs, including hepatocellular carcinoma (HCC) (n = 107), liver metastasis (n = 21), intrahepatic cholangiocarcinoma (ICC) (n = 7), liver hemangioma (n = 37), focal nodular hyperplasia (FNH) (n = 11), regenerative nodule (n = 6) and liver lipoma (n = 1). The cadence contrast pulse sequencing technique and the contrast agent SonoVue(R) were used for CEUS examination. The enhancement patterns during the arterial, portal, and late phases were evaluated. HCC showed hyperenhancement in 100 (93.5%) of 107 nodules during the arterial phase and hypoenhancement in 102 (95.3%) during the late phase. Liver metastases showed homogeneous enhancement in 8 of 21 (38.1%) nodules and a peripheral regular rim-like enhancement in 11 of 21 (52.4%) nodules during the arterial phase and marked hypoenhancement in 16 of 21 (76.2%) nodules during the late phase. ICC exhibited irregular rim-like enhancement in 4 of 7 (57.1%) nodules during the arterial phase and hypo-enhancement in 7 of 7 (100%) nodules during the late phase. Hemangioma showed peripheral nodular hyperenhancement, and progressive centripetal enhancement was seen in 35 of 37 (94.6%) lesions during the arterial phase. All 11 cases of FNH exhibited homogeneous hyperenhancement during the arterial phase and hyperenhancement (n = 1) or isoenhancement (n = 9) during the late phase. The sensitivity, specificity, and positive predictive value, respectively, were 88.8%, 89.2%, and 91.3% for HCC; 81%, 100%, and 100% for liver metastasis; 57.1%, 100%, and 100% for ICC; 94.6%, 100%, and 100% for liver hemangioma; and 90.9%, 97.8%, and 71.4% for FNH. Low-mechanical index CEUS permits real-time, complete assessment of vascularity in FLLs, which in turn facilitates their characterization.