This study supports that testing for CLDN18.2 positivity can aid in identifying patients who may benefit from CLDN18.2-targeted therapy with zolbetuximab, and that testing for CLDN18.2 positivity in all histologic subtypes should be incorporated into routine biomarker testing along with testing for HER2, PD-L1, and microsatellite instability for patients with LA unresectable or mG/GEJ adenocarcinoma. Here, CLDN18 is linked to gastroesophageal junction adenocarcinoma.