Decreased expression of the intercellular adhesion molecule E-cadherin correlates with tumor aggressiveness and invasion capacity of cell lines. The decrease of E-cadherin expression results primarily from reduced mRNA expression. We show here that the activity of a human E-cadherin promoter construct is cell specific and correlates with E-cadherin mRNA expression. This spectrum of activity is conserved by a region as short as 81 bp obtained after 5' deletion. Mutation analysis revealed that two E box elements of this minimal promoter are involved in the silencing of E-cadherin promoter activity occurring in cancer cells. E boxes are mainly known as target sequences for bHLH transcription factors that are involved in the control of tissue differentiation and are antagonised by HLH proteins. However, mutation data and cotransfection experiments using HLH protein expression vectors indicate that bHLH transcription factors are not significantly involved in the E box mediated silencing of this E-cadherin promoter fragment.