In the United States, cirrhotic patients with known or suspected hepatocellular carcinoma (HCC) are prioritized for liver transplantation. Noninvasive criteria for the diagnosis of HCC rely on arterial enhancement of a mass. The aim of this study was to determine whether clinical, laboratory, and / or radiologic data can improve the prediction of HCC in cirrhotic patients with an arterially-enhancing mass. Between May 2002 and June 2003, dynamic gadolinium-enhanced magnetic resonance imaging (MRI) of consecutive patients with liver cirrhosis and a solid mass were reviewed by 2 radiologists blinded to the clinical diagnosis. Clinical, laboratory, and radiologic data were recorded for all patients. A total of 94 patients with cirrhosis and an arterially-enhancing liver mass were studied, 66 (70%) of whom had HCC. Alpha-fetoprotein (AFP) >20 ng/mL (P = .029), tumor size >2 cm (P = .0018), and delayed hypointensity (P = .0001) were independent predictors of HCC. Delayed hypointensity of an arterially-enhancing mass had a sensitivity of 89% and a specificity of 96% for HCC. The presence of delayed hypointensity was the only independent predictor of HCC among patients with arterially-enhancing lesions <2 cm (odds ratio, 6.3; 95% confidence interval [CI], 1.8-13), with a sensitivity of 80% and a specificity of 95%. In conclusion, delayed hypointensity of an arterially-enhancing mass was the strongest independent predictor of HCC, regardless of the size of the lesion. If additional studies confirm our results, the noninvasive criteria utilized to make a diagnosis of HCC should be revised.