WNT genes encode secreted growth factors with potent stem cell activities. Deregulation of WNT expression and signaling is frequently observed in various cancers, making this signaling pathway a particularly attractive target for treatment of cancer. Here we show that a single WNT gene, WNT5A, produces two proteins that have distinct activities in human tumors. We also show that these two WNT5A isoforms may have prognostic value for survival of several cancer types.