Endoscopic biopsy sampling of a gastric or GEJ mass is no longer just for histologic diagnosis. The biopsy material may be used for ancillary IHC and/or DNA testing. When possible, multiple biopsy specimens for sampling different areas of the tumor should be obtained to provide the best opportunity to identify overexpression of HER2 and abnormalities in other genes/proteins that may be expressed in different areas of the tumor. Thorough sampling at the time of initial diagnosis may prevent the need for future endoscopic procedures for the sole purpose of obtaining additional tissue for biomarker studies. Communication and coordination with oncologists and pathologists is essential to ensure an appropriate HER2 evaluation is performed. In the coming age of targeted therapeutics, endoscopy may not only be used to obtain tissue for histology and biomarker evaluation but may also be used for the direct in vivo evaluation of biomarkers that guide therapy.