To provide insights for CEA-targeted diagnostics and therapy and understand the specificity of anti-CEA mAbs, many efforts have been made to characterize the binding epitopes of these antibodies using various approaches [49, 50, 51, 52] . The most extensive investigations involve the classification of 52 anti-CEA mAbs into five distinct epitopes, Gold epitopes 1-5, by competitive binding analysis [50] . Further studies have correlated the Gold epitopes to the domains of CEA using different CEA fragment constructs [51, 53, 54] , however there is no precise localization of the epitopes to the amino acid sequence level. An attempt to identify the amino acid sequences corresponding to Gold epitopes using synthetic overlapping fifteen-mer peptides has failed [55] , suggesting that the Gold epitopes are conformational. In addition, immunohistochemistry and immuno flow cytometry were used to demonstrate a good correlation between the Gold epitope groups and their binding specificity: 1) mAbs that bind to Gold epitopes 2 and 3 were generally specific to CEA, reacting only with colon carcinoma, normal colon mucosa and normal gastric foveola; 2) mAbs in epitopes 4 and 5 were highly cross-reactive with different normal tissues possibly due to binding to CEA-related antigens; and 3) both specific and cross-reactive mAbs were found in epitope 1 [56] . We have mapped the epitope of the CEA-specific arm of MEDI-565 to the A2 domain comprised of two stretches of amino acids, 326-349 and 388-410. Interestingly, the MEDI-565 epitope on CEA belongs to the Gold epitope 2, which has been localized in the A2-B2 domains [53] and identified as a CEA-specific epitope group [56] .