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Breast conserving surgery, in which the breast tumor and the surrounding normal tissue are removed, is the primary mode of treatment for invasive and in situ carcinomas of the breast, conditions that affect nearly 200 000 women annually. Of these nearly 200 000 patients who undergo this surgical procedure, between 20%-70% of them may undergo additional surgeries to remove tumor that was left behind in the first surgery, due to the lack of intraoperative tools that can detect whether the boundaries of the excised specimens are free from residual cancer. Optical techniques have many attractive attributes that may make them useful tools for intraoperative assessment of breast tumor resection margins. In this paper, we discuss clinical design criteria for intraoperative breast tumor margin assessment and review optical techniques applied to this problem. In addition, we report on the development and clinical testing of quantitative diffuse reflectance imaging (Q-DRI) as a potential solution to this clinical need. Q-DRI is a spectral imaging tool, which has been applied to 55 resection margins in 48 patients at Duke University Medical Center. Clear sources of contrast between cancerous and cancer-free resection margins were identified with the device, and resulted in an overall accuracy of 75% in detecting positive margins.