These data suggest that at least some forms of gastric cancer may arise from Lgr5-expressing stem cells; identify iLgr5;GLI2A mice as a novel model of invasive gastric adenocarcinoma; support the notion that deregulated Hh/GLI signaling may contribute to human gastric tumorigenesis; and point to an important role for deregulated mTOR signaling, likely via the mTORC1 complex, acting downstream of GLI2A in this model. Here, LGR5 is linked to gastric adenocarcinoma.