Physical Sciences, Inc. (PSI), in collaboration with Massachusetts General Hospital proposes to investigate the use of a high sensitivity/specificity cancer targeting agent and of a novel fluorescence-guided microscopy (FGM) scheme for intraoperative assessment of surgical margins in breast cancer patients. The contrast agent will be used to label cancer cells and highlight positive margins on lumpectomy specimens. FGM will then be used to visualize tissue morphology at the cellular scale and provide the pathologist with histology-like images to confirm or rule out cancer presence. In Phase I we propose to develop, test, and optimize a suitable contrast agent for cancer labeling and a benchtop instrument that will combine fluorescence imaging and high resolution/penetration depth coherence microscopy within the same optical platform with automated dual modal image registration. Preliminary testing of this technology will be performed on several surgical specimens. Based on Phase I conclusions, this technology will be improved during a Phase II study and tested in a clinical setting at the Massachusetts General Hospital.