Dog1 is a cell surface protein of unknown function selectively expressed in gastrointestinal stromal tumors (GIST). Among GIST cases with KIT mutations the Dog1 antibody identified 11% more cases than c-Kit antibody. Dog1 identifies vast majority of both c-Kit negative and PDGFRA mutated GIST cases that may still benefit from imatinib mesylate (Gleevac), an inhibitor of the kit tyrosin kinase. In addition, Dog1 immunoreactivity is seen in fewer cases of mesenchymal, epithelial tumors and melanomas when compared with c-Kit. The use of this highly sensitive and specific novel marker will increase the accuracy of GIST diagnosis.