Cell adhesion molecule 2 (CADM2) is an immunoglobulin (Ig)-like cell adhesion molecule, which belongs to the CADMs family. The four members of CADMs family including three Ig-like domains and a short cytoplasmic tail share high degree of identity with each other, making it difficult to specifically identify each members using western blotting or immunohistochemistry. And most of anti-CADM2 antibodies available commercially or used in published papers are rabbit polyclonal antibodies, exhibiting nonspecific recognition in studies. In this study, we developed a monoclonal antibody (mAb) specific to an epitope on the extracellular domain of CADM2 using conventional hybridoma technology. Western blot assays indicated that the established mAb, named as 2B11, was specific for CADM2 recognition without interference of other members of CADMs family. Furthermore, 2B11 was competent to detect CADM2 expression specifically on the surface membranes of several types of tumor tissues, avoiding the false results with the polyclonal antibodies due to nonspecific staining. In conclusion, the mAb 2B11 could be suitable for specific detection of CADM2 expression in tumor cells or tissues.