PURPOSE:To evaluate whether diffusion-weighted imaging (DWI) improves the detection of hepatocellular carcinoma (HCC) on super paramagnetic iron oxide (SPIO)-enhanced MRI. MATERIALS AND METHODS:This retrospective study group consisted of 30 patients with 50 HCC nodules who underwent MRI at 1.5 Tesla. Two combined MR sequence sets were compared for detecting HCC: SPIO-enhanced MRI (axial T2-weighted fast spin-echo (FSE) and T1-/T2*-weighted fast field echo (FFE) scanned before and after administration of ferucarbotran) and SPIO-enhanced MRI + DWI (SPIO-enhanced MRI with axial DWI scanned before and after administration of ferucarbotran). Three blinded readers independently reviewed for the presence of HCC on a segment-by-segment basis using a four-point confidence scale. The performance of the two combined MR sequence sets was evaluated using receiver operating characteristic (ROC) analysis. RESULTS:The average area under the ROC curve (Az) of the three readers for the SPIO-enhanced MRI + DWI set (0.870 +/- 0.046) was significantly higher that that for the SPIO-enhanced MRI set (0.820 +/- 0.055) (P = .025). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detection of HCC were 66.0%, 98.0%, 90.0%, and 91.4%, respectively, for the SPIO-enhanced MRI set, and 70.0%, 98.6%, 92.9%, and 92.4%, respectively, for the SPIO-enhanced MRI + DWI set. CONCLUSION:The SPIO-enhanced MRI + DWI set outperformed the SPIO-enhanced MRI set for depicting HCC.