High resolution positron emission mammography (PEM) can address the current clinical needs of breast cancer patients and the requirements for future translational work. Combining the quantitative capabilities of positron emission tomography (PET) with millimeter resolution, PEM can image the earliest in situ forms of breast cancer as well as putative cancer precursor lesions (e.g., atypical ductal hyperplasia) whose behavior is important for prevention studies. The importance of the ability to detect intraductal cancer cannot be overemphasized, for several reasons: at least one-third of new cancers are detected at this intraductal stage, intervention at this stage represents the best opportunity for complete cure, and a significant number of invasive cancers contain an intraductal component. Without knowledge of the extent of the intraductal component, surgeons are unable to completely excise cancers about a third of the time, leading to unnecessary re-excisions or radiation therapy. Current investigations aimed at specifying best practices in radiotherapy of DCIS patients are stymied by the lack of objective quantitative methods of rapidly assessing response. Other future applications of PEM are suggested, including an information technology project built on PEM that promises to individualize therapy and facilitate surveillance of high risk populations. The high overall accuracy of PEM (i.e., both specificity and sensitivity) is an unusual and welcome development in the history of breast imaging. With this high accuracy, and continued technical innovation to reduce radiation dose, PEM may someday replace X-ray mammography as a first line approach to breast cancer detection.