This study shows that circulating tumor cells, before dissemination from a primary tumor, are empowered to escape NK cell surveillance and form metastasis by cross‐talking with mesenchymal stromal cells in the tumor microenvironment via an intercellular cGAS‐cGAMP‐STING‐IFNβ‐HLA‐I signaling loop. The gene discussed is STING1; the disease is neoplasm.