The Wnt-5A gene codes for a secreted cysteine-rich growth factor that mediates cell to cell signaling via a paracrine mechanism during development and ontogeny. We have recently determine the genomic organization and chromosomal mapping of the human Wnt-5A, and observed distinct patterns of expression in developing human embryos. In this report, we have performed a detailed expression analysis of 100 adult human tissues and tumors and 10 human cell lines. Our data show a widespread expression of Wnt-5A in adult tissues and cells, and aberrant mRNA levels in lungs, breast, and prostate carcinomas and in melanomas. The up-regulation of Wnt-5A in human malignancy was not due to either gene rearrangement or amplification. These findings document an abnormal expression of this growth factor in malignancy and implicate Wnt-5A in the genesis of human cancer.