The aim of this study was to assess the added diagnostic value of contrast-enhanced US (CEUS) combined with 64-row multidetector CT (CT) in the assessment of hepatocellular nodule vascularity in patients with liver cirrhosis. One hundred and six cirrhotic patients (68 male, 38 female; mean age +/- SD, 70 +/- 7 years) with 121 biopsy-proven hepatocellular nodules (72 hepatocellular carcinomas, 10 dysplastic and 15 regenerative nodules, 12 hemangiomas, and 12 other benignancies) detected during US surveillance were prospectively recruited. Each nodule was scanned by CEUS during the arterial (10-40 s), portal venous (45-90 s), and delayed sinusoidal phase (from 100 s after microbubble injection to microbubble disappearance). Nodule vascularity at CEUS, CT, and combined CEUS/CT was evaluated side-by-side by two independent blinded readers who classified nodules as benign or malignant according to reference diagnostic criteria. The combined assessment of CEUS/CT provided higher sensitivity (97%, both readers) than did separate assessment of CEUS (88% reader 1; 87% reader 2) and CT (74% reader 1; 71% reader 2; P < 0.05), while no change in specificity was provided by combined analysis. The combined assessment of hepatocellular nodule vascularity at CT and CEUS improved sensitivity in the diagnosis of malignancy in patients with liver cirrhosis.