Colorectal and pancreatic cancers together comprise the third and fourth most common causes of cancer-related death in the United States. In either type of cancer detection of both primary and metastatic disease is critical to patient survival. We have investigated the use of a fluorophore-labeled anti-CEA monoclonal antibody to aid in cancer visualization in nude mouse models of human colorectal and pancreatic cancer. Monoclonal anti-CEA was conjugated with AlexaFluor 488. In vitro staining demonstrated positive CEA expression in five human pancreatic cancer cell lines (ASPC-1, BxPC-3, Panc-1, CFPAC and CAPAN-1) and four human colon cancer cell lines (HCT-116, LS174T, SW948 and LOVO). Ten days after subcutaneous injection of either ASPC-1, BxPC-3 or LS174T cells into athymic mice, 100 μg conjugated antibody was delivered via tail vein injection. Small (1-2 mm diameter) subcutaneous tumors were clearly visible with bright green fluorescence after skin-flap elevation 24 hours after administration of the labeled antibody. Figure upper panels show representative in vitro staining, lower panels show subcutaneous tumor staining (scale bar 10mm). The signal remained present for at least eight days. In addition, a primary human colon cancer specimen originally harvested from a liver metastasis was passaged several times in nude mice. This tumor tissue was also analyzed for in vivo staining with the fluorohopre-conjugated anti CEA and stained strongly positive in a subcutaneous model. These results indicate that fluorophore-labeled anti-CEA offers a novel intra-operative imaging technique for the enhanced visualization of tumor in both colorectal and pancreatic cancer when CEA expression is present.