OBJECTIVE We evaluated the usefulness of contrast-enhanced harmonic gray scale ultrasonographic findings for differential diagnosis of gallbladder diseases. METHODS We evaluated contrast-enhanced harmonic gray scale ultrasonographic images from 33 patients with 35 polypoid gallbladder disease lesions larger than 10 mm in diameter, consisting of 12 biliary sludge lesions, 8 cholesterol polyps, 1 inflammatory polyp, 2 adenomas, and 12 carcinomas. After a galactosepalmitic acid contrast agent was injected, lesions were scanned by contrast-enhanced harmonic gray scale ultrasonography in 2 phases: early vascular and late vascular. RESULTS None of the biliary sludge lesions (n = 12) showed either tumor vessels or tumor enhancement. Lesions showing tumor vessels and tumor enhancement on contrast-enhanced harmonic gray scale ultrasonography were diagnosed as cholesterol polyp, inflammatory polyp, adenoma, or carcinoma. Three (38%) of the 8 cholesterol polyps showed dotted-type tumor vessels. Branched-type tumor vessels were observed in 5 (62%) of the 8 cholesterol polyps, the 1 (100%) inflammatory polyp, both (100%) adenomas, and 3 (25%) of the 12 carcinomas. Tortuous-type tumor vessels were observed in 9 (75%) of the 12 carcinomas. Lesions with tumor enhancement and tortuous-type tumor vessels on contrast-enhanced harmonic gray scale ultrasonography were diagnosed as carcinomas, and the sensitivity, specificity, and accuracy of this diagnosis with the current modality were 75% (9/12), 100% (23/23), and 91% (32/35), respectively. CONCLUSIONS Evaluation of tumor vessels on contrast-enhanced harmonic gray scale ultrasonography may be a useful modality for differentiating gallbladder carcinoma from other polypoid gallbladder disease lesions.