Breast ultrasound is generally interpreted with knowledge of the mammographic examination. This study examined the influence of knowledge of mammography findings on the accuracy of ultrasound in women with breast symptoms. Subjects were sampled from all women 25-55 years of age consecutively attending a breast clinic. This included all 240 women shown to have breast cancer and 240 age-matched women shown not to have cancer. Ultrasound films were prospectively reviewed and reported by two radiologists independent of each other and in a blinded manner. A two-phase design was used. In the first phase, the radiologists provided an opinion on the ultrasound films. In the second phase, the ultrasound films were reread with consideration of the corresponding mammographic examination. The accuracy of reading the ultrasound with and without knowledge of the findings on mammography was compared using sensitivity and specificity, and receiver operating characteristics (ROC) curves. Reporting the ultrasound with knowledge of mammography (compared to without mammography) improved sensitivity and reduced specificity for both radiologists. For one reader, sensitivity increased from 77.5% to 86.7% (p = 0.0002) and specificity decreased from 89.7% to 85.4% (p = 0.04). For the other reader, sensitivity increased from 81.3% to 87.5% (p = 0.0023) and specificity decreased from 87.1% to 85.0% (p = 0.27). ROC curves for both radiologists showed that reporting ultrasound with knowledge of mammography resulted in small (about 3%), but significant improvement in the area under the ROC curve. Our study indicates that knowledge of the findings of mammography improves the interpretation of breast ultrasound in symptomatic women.