LGR5 is an orphan G-protein-coupled receptor (GPCR) that is expressed on the cell surface membrane LGR5 is reported to be overexpressed in colon, liver, and ovary tumor compared to normal tissue However, a specific ligand for LGR5 has not yet been determined, and the function is still not clear An LGR5-specific monoclonal antibody (mAb) is needed as a tool for detection and analysis of LGR5 biological function and cancer therapy. To date, no mAb against LGR5 that retains high affinity and specificity has been reported Here, we report successful establishment and characterization of a mAb (KM4056) that specifically recognizes the extracellular N-terminal domain of human LGR5, but not LGR4 or LGR6 This mAb has potent complement-dependent cytotoxicity (CDC) activity in vitro and shows strong anti-tumor activity in vivo against xenograft model by transplanting LGR5 expressing CHO transfectants into SCID mice Thus, KM4056 can be a useful tool for detection of LGR5 positive cells and analysis of LGR5 biological function (C) 2010 Elsevier Inc All rights reserved