The purpose of this study is to evaluate the accuracy of image volume based registration (IVBaR) of 3D ultrasound (US) image volumes of the whole breast acquired at different times. Successful IVBaR could aid in detection of tumor changes in response to neoadjuvant chemotherapy and potentially be useful for routine breast cancer screening and diagnosis. IVBaR was successful in 9 of 10 reproducibility studies, 11 of 15 image pairs collected before and after approximately 45 days of chemotherapy. Doppler study yielded volume of blood flow to the region surrounding the lesion and its change when reducing breast compression. The color flow vessels provided independent measures for validation of registration of the grayscale portion of those images.