Uncovering the signalling pathways by which growth factors regulate epithelial–mesenchymal transition (EMT) could guide the development of new therapies for cancer metastasis. Gujral et al. found that the WNT receptor Frizzled 2 (FZD2) and its ligands WNT5a and WNT5b are elevated in human samples of metastatic tumours. A pharmacological and genetic screen in cancer cell lines revealed that FZD2 drives EMT and cell migration through a new, non-canonical pathway that includes FYN and STAT3. Reducing FZD2 expression by RNA interference or blocking the activity with anti-FZD2 antibodies reduced WNT5-mediated cell migration in vitro and inhibited tumour growth and metastasis in a mouse xenograft model.