Non-invasive differentiation of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) is difficult. The aim of this study was to assess the accuracy of contrast-enhanced phase inversion ultrasound to differentiate between histologically proven FNH and HCA, analysing the arterial and (early) portal venous phase. 32 patients with histological proven FNH (n=24) or HCA (n=8) have been included in this prospective study. Examination technique: Siemens Elegra, phase inversion harmonic imaging (PIHI) with low mechanical index (MI)<0.2-0.3 using SonoVue (BR 1). The contrast enhancing tumour characteristics were evaluated during the hepatic arterial (starting 8-22 s) and early portal venous phase (starting 12-30 s). The image analysis was performed by three examiners. In 23 of 24 patients with FNH the contrast pattern revealed pronounced arterial and (early) portal venous enhancement. Homogeneous enhancement was detected during the hepatic arterial phase in all eight patients with HCA. In contrast to patients with FNH, no enhancement was seen during the portal venous phase. In conclusion, contrast-enhanced phase inversion ultrasound demonstrated pronounced arterial and portal venous enhancement in patients with focal nodular hyperplasia. In contrast, after homogeneous enhancement during hepatic arterial phase, no enhancement during hepatic portal venous phase was detected in patients with hepatocellular adenoma. Therefore, this technique might improve the functional characterization of benign hypervascular focal liver lesions.