Approximately one in eight women in the United States will develop breast cancer in their lifetime.1 An estimated 207,000 new cases of breast cancer will be diagnosed in the United States in the next year, and approximately 40,000 U.S. women will die of this disease in the same period.2 Currently, histologic assessment is the gold standard for differentiating neoplastic from non-neoplastic lesions to diagnose breast cancer. However, histologic assessment has limitations including the requirement for extensive tissue processing, and it takes several days to complete preparation before samples can be assessed by pathologists. Furthermore, if cores or tissue excised are inadequate for clinical diagnosis or research applications, an additional tissue excision procedure must be performed. Frozen section pathology can be performed the same day of tissue excision;3,4 however, frozen section has shown to be limited by sampling variability, which can lead to false negatives.5,6 Breast pathology experts in the United States7 and Europe8,9 do not recommend frozen section for breast lesions which cannot be identified by macroscopic examination, which are smaller than 10 mm in size, and for which a preoperative diagnosis is not possible.7,8,10 Fine needle aspiration cytology can also be used for rapid breast lesion assessment,5,8 but does not preserve tissue architecture in the context of the lesion microenvironment. There is a need for a rapid technique that provides high-resolution morphologic detail to differentiate neoplastic from non-neoplastic breast lesions in real time and to inform the management of breast disease.