Trends toward earlier detection, image-guided biopsy techniques and less disfiguring surgeries have dramatically improved the lives of breast cancer patients. The non-invasive ablation of both benign and malignant breast cancer represents the next major improvement in the treatment of breast cancer, destroying the primary tumor with the least traumatic and best possible cosmetic outcome for the patient. Several thermal-based technologies are being investigated to accomplish this goal, but to date these approaches have been limited in their applicability. We have developed and tested a novel non-invasive ultrasonic technology that utilizes pulsed, focused ultrasound to generate non-thermal mechanical effects within a targeted tissue volume. We call this technology soft tissue lithotripsy or “histotripsy”. Preliminary results of transcutaneous ablation are very promising. Within the target zone, a cavity is produced that contains a liquefied core with smooth walls and sharply demarcated boundaries. Histology demonstrates extensive areas of acellular debris with no remaining cellular structure, surrounded by an almost imperceptibly narrow margin of cellular injury. This extremely sharp transition zone, impossible with thermal therapy, may allow for the complete ablation of a breast tumor with minimal damage to the normal breast tissue. The probability of attaining this goal is also enhanced by the demonstrated ability to clearly see this tissue damage boundary during or after the histotripsy procedure, an aspect of thermal therapy that has been difficult to attain.