LGR4/5/6 proteins play critical roles in development and cancer. The biological functions of these proteins have been primarily attributed to their roles in potentiating Wnt signaling. The mosaic photo illustrates widespread lung metastases in mice xenografted with green fluorescence–labeled human breast cancer cells expressing LGR4 mutants that cannot potentiate Wnt signaling, revealing that LGR4 promotes metastasis even when disengaged from Wnt signaling. For details, see article by Yue and colleagues on page 4441.