Thirteen cases of primary adenocarcinoma of the gallbladder (GB), 1 of malignant fibrous histocytoma, 3 of metastatic adenocarcinoma, 5 of adenoma, 5 of polypus, 2 of xanthogranuloma, 6 of chronic cholecystitis, 4 of acute cholecystitis, and 8 of subacute cholecystitis were studied by image-directed and color Doppler ultrasonography (CDUS). All of the 14 cases of primary GB cancer (10 masses, 4 thickening wall) were found to have a high velocity arterial blood flow signal in the wall of the GB. In contrast, the 3 cases of metastatic cancer of the GB had no blood flow signal in the wall of the GB. For the 30 cases of benign lesions of the GB, only in 12 cases was a low velocity blood flow signal found. Nine of 10 cases of primary GB malignancy were found to have high velocity arterial blood flow signals in the tumor masses. No blood flow signal was observed in the masses of 13 cases (3 of metastatic adenocarcinoma, 5 of adenoma, 5 of polypus). An abnormal high velocity arterial blood flow signal observed within masses in the GB or in the GB wall is a significant feature of primary GB cancer and thus helps to differentiate primary GB cancer from metastatic and benign lesions of the GB.