The purpose of this study was to test the efficacy of using small training sets in computer-aided diagnostic systems (CAD) and to increase the capabilities of ultrasound (US) technology in the differential diagnosis of solid breast tumors. A total of 263 sonographic images of solid breast nodules, including 129 malignancies and 134 benign nodules, were evaluated by using a bootstrap technique with 10 original training samples. Texture parameters of a region-of-interest (ROI) were resampled with a bootstrap technique and a decision-tree model was used to classify the tumor as benign or malignant. The accuracy was 87.07% (229 of 263 tumors), the sensitivity was 95.35% (123 of 129), the specificity was 79.10% (106 of 134), the positive predictive value was 81.46% (123 of 151), and the negative predictive value was 94.64% (106 of 112). This analysis method provides a second opinion for physicians with high accuracy. The new method shows a potential to be useful in future application of CAD, especially when a large database cannot be obtained for training or a newly developed ultrasonic system has smaller sets of samples.