Expression of the E-cadherin cell adhesion molecule is reduced in several types of human carcinomas, and the protein serves as an invasion suppressor in vitro. To determine if mutations of the E-cadherin gene (on chromosome 16q22) contribute to epithelial tumorigenesis, 135 carcinomas of the endometrium and ovary were examined for alterations in the E-cadherin coding region. Four mutations were identified: one somatic nonsense and one somatic missense mutation, both with retention of the wild-type alleles, and two missense mutations with somatic loss of heterozygosity in the tumour tissue. These data support the classification of E-cadherin as a human tumour suppressor gene.