Systems and methods are provided by which a mammography imaging system offers X-ray and ultrasound imaging that allows sharing of common hardware such as the computer and display. Small regions of interest are imaged with X-ray at higher image quality by using a second sensor with higher DQE than the full-field sensor can obtain. In some embodiments a specialized chamber is provided for securing the anatomy to a fixed location, ultrasound image data is collected along with ultrasound probe location and orientation data from sensors on a handheld probe from which data images can be viewed directly, or used to reconstruct tomographic images of any desired cross-section, or used for various " 3 -D" image visualization methods. An imaging schedule defined by location and orientation of an ultrasound probe is used to generate a three-dimensional ultrasound image.