A newly identified gene, H-cadherin, is reported. H-cadherin encodes a protein related to the cadherin superfamily of cell adhesion molecules, and its expression is shown to be significantly reduced in human breast carcinoma cell lines and breast cancer specimens. H-cadherin was localized to chromosome 16q24 and is highly expressed in the heart. Introduction of H-cadherin cDNA markedly diminished tumor cell growth and resulted in a significant change from invasive morphology to a normal cell-like morphology in the Matrigel outgrowth assay. These studies indicate that downregulation of H-cadherin may be frequent in the breast malignant progression and suggest that it may have prognostic value as a marker for breast cancer development.