Aberrant expression of polypeptide N-acetyl-galactosaminyltransferases (GALNTs) has been associated with cancer, but their function(s) in metastasis remains elusive. Recently, we have identified GALNT14, one of the O-GalNAc glycosylation-initiating enzymes, as a prognostic marker for pulmonary relapses in breast cancer patients. Furthermore, we showed that GALNT14 promotes lung metastasis by novel mechanisms: 1) enhancing metastasis initiation by inhibiting anti-metastatic effect of BMPs produced from lung stroma, 2) exploiting growth signals (e.g., FGFs) supplied by macrophages for their growth into macrometastases in the lung environment. These multi-faceted roles of GALNT14 in lung metastasis are achieved by GALNT14-mediated inhibition and activation of BMP and FGF signaling pathways, respectively. The link among GALNT14, its downstream pathways and lung metastasis provides us with an opportunity to develop effective therapeutic intervention for breast cancer.