Objectives: Currently, the primary treatment for solid tumors is the sur- gical resection. In the surgery, the complete surgical resection of the cancer tissues is essential to the prognosis of cancer patients. However, even in US, 40% of the cancer patients have the local recurrence in 5 years from the initial surgery, due to the failure to detect all the cancer tissues intraoperatively since cancers are highly heterogeneous in surface morphology and anato- mical structures. We designed a novel visible/near-infrared (VIS/NIR) quan- titative imaging method to help surgeons improve pancreatic cancer resec- tion by providing quantitative intraoperative cancer diagnosis. Method: All the clinical studies were performed according to an approved protocol by the Emory Institutional Review Board (protocol #: IRB00053609). Before the surgery, the patient receives an intravenous injection of indocyanine green (ICG). After 3-8 hours, the tissues of interest, are inspected intraoperatively with our lab-developed VIS/NIR imaging system. The VIS/NIR imaging system consists of two parts: a) a portable VIS/NIR camera imaging system for quick detection of potential cancers; b) a hand-held spectroscopic device for quantitative tissue assessment. Two IEEE 1394 cameras were assembled into an optical tube platform (Thorlabs, USA) to record VIS and NIR signals simultaneously. Results: We have conducted dozens of clinical trials on human pancreatic cancer in Emory University Hospital and Saint Joseph's Hospital in Atlanta, GA, USA. Over two hundred sample tissues from various pancreatic cancer sur- geries, including distal pancreatectomy, Whipple procedure, and total pan- createctomy, were inspected with our imaging system. Within 1 sec, our device can quantitatively differentiate cancerous tissues from non-cancerous tissues intraoperatively: primary tumor and positive margins showed more than 200% stronger ICG fluorescence than normal tissues and negative margins did. The overall diagnosis accuracy of pancreatic cancer by our system is 93.7%. Conclusion: In summary, we developed a comprehensive imaging system to provide surgeons with instantaneous (o1sec) cancer identifi- cation intraoperatively, compared to the traditional lengthy histopatho- logical consultation (20-30mins for intraoperative frozen section proce- dure with lower diagnosis accuracy, or hours-days for postoperative for- malin fixed paraffin-embedded tissue preparation). Compared to the other reported imaging systems, our system has a unique advantage in providing quantitative NIR spectral analysis on the tissues of interest. This feature makes it possible to differentiate many tissues that current pre- vailing camera imaging systems cannot distinguish. This work was supported by the Transformative R01 program (R01 CA163256) and the Grand Opportunity (GO) grant (RC2 CA148265) from the National Institutes of Health, a part of the U.S. Department of Health and Human Services.