We investigated mutations of the epithelial (E)-cadherin gene and loss of heterozygosity (LOH) at flanking loci using three microsatellite markers on the long arm of chromosome 16 in 25 ductal carcinomas of the breast. Expression of E-cadherin was also investigated immunohistochemically. No mutations were detected in exons 6 through 9 of the E-cadherin gene. LOH was observed more frequently (42%) at D16S402 (16q-ter) than at D16S421 (16q22.3-q23.1) (17%), which is located near the E-cadherin gene. Expression of E-cadherin was observed at the cell borders in 92% (11/12) of the tumors examined. The absence of mutations in the E-cadherin gene and its conserved expression suggest that inactivation of E-cadherin does not contribute significantly to the invasion or metastatic potential of ductal carcinomas of the breast. Furthermore, the high frequency of LOH at 16q-ter suggests the existence of another tumor suppressor gene which may play a crucial role in the genesis of ductal carcinomas of the breast.