OBJECTIVE To evaluate the usefulness of contrast-enhanced harmonic wideband gray scale sonographic images obtained after radio frequency-induced coagulation necrosis, we compared the morphologic and histopathologic characteristics of the ablated tumors with sonographic images of the tumors. METHODS Forty-eight patients with 72 hepatocellular carcinomas with a maximal diameter of 3 cm or less were treated percutaneously using radio frequency ablation. Six treated tumors in 4 patients were resected 1 month after ablation; the remaining 66 treated tumors were evaluated by a biopsy procedure performed with an 18-gauge fine needle 1 month after ablation. The excised tumors and biopsy specimens were then examined by histopathologic methods, and the findings were compared with those obtained on contrast-enhanced harmonic wideband gray scale sonography. Hematoxylin-eosin-stained specimens were inconclusive as to whether cellular viability remained; therefore, cell viability was determined by a positive result after histochemical (lactate dehydrogenase and nicotinamide adenine dinucleotide phosphate-diaphorase) staining. RESULTS Contrast-enhanced harmonic wideband gray scale sonography after radio frequency ablation showed residual tumor enhancement in 5 (6.9%) of the 72 tumors; the histopathologic results for these 5 tumors were also positive for tumor residue. The remaining 67 tumors (93.1%) did not show any residual tumor enhancement when examined by sonography; however, only 66 tumors did not reveal tumor residue when examined histopathologically. Contrast-enhanced harmonic wideband sonographic imaging provided results that were comparable with histopathologic findings, the criterion standard for diagnosis; the sensitivity and specificity of the sonographic images for the detection of residual tumor tissue in ablated tumors were 83.3% (5 of 6) and 100% (66 of 66), respectively. CONCLUSIONS Contrast-enhanced harmonic wideband gray scale sonography is a potentially useful technique for evaluating the therapeutic effects of radio frequency ablation on hepatocellular carcinoma.