The purpose of this preference study is to determine if tissue harmonic imaging (THI) is preferred over conventional sonography for imaging breast masses. A prospective evaluation of 73 identical image pairs (one obtained with conventional sonography, one with THI sonography) was performed, examining 25 cysts, 36 solid masses, and 12 indeterminate lesions. Each image was evaluated for lesion contrast, margins, and overall image quality using a graduated score. Statistical analysis was performed using a modified t test. For cystic and solid lesions, THI was preferred for lesion conspicuity, margin, and overall quality (P<.001). For indeterminate lesions, THI was significantly preferred for lesion conspicuity and overall quality (P<.05), but the preference for margins was not significant. Overall, THI of breast lesions was significantly preferred for lesion contrast and margin evaluation compared to conventional sonography. This modality deserves further evaluation and may improve detection and evaluation of breast lesions.