Although it is believed that altered conformations exposing cryptic regions are intermediary and critical steps in the mechanism of transthyretin (TTR) amyloid formation, no effective therapy targeting this step is available. In this study, to establish the antibody therapy for familial amyloidotic polyneuropathy (FAP), we generated a monoclonal anti-TTR antibody, which specifically reacts with surface epitopes of TTR (MAb ATTR) and evaluated its binding affinity and specificity for TTR amyloid fibrils. MAb ATTR showed specific binding affinity for TTR amyloid fibrils, but not for native form of TTR. Moreover, MAb ATTR indeed showed the high consistency with Congo red positive areas in tissue specimens from FAP ATTR V30M patients, indicating that MAb ATTR showed binding affinity and specificity for TTR amyloid fibrils in vitro and in vivo. MAb ATTR may have a potential to suppress TTR amyloid deposition and become a candidate for the antibody therapy for FAP.