Human carcinoembryonic antigen (CEA), a widely used tumor marker, and CEACAM6 [formerly nonspecific cross-reacting antigen (NCA)] are up-regulated in many types of human cancers, whereas family member CEACAM1 [formerly biliary glycoprotein (BGP)] is usually down-regulated. Deregulated overexpression of CEA/CEACAM6 but not CEACAM1 can inhibit the differentiation and disrupt the polarization and tissue architecture of many different types of cells. In this report, we show that CEA and CEACAM6, but not CEACAM1, markedly inhibit the apoptosis of cells when deprived of their anchorage to the extracellular matrix, a process known as anoikis. By blocking this tissue architecture surveillance mechanism, the architectural perturbation initiated by CEA/CEACAM6 can thus be maintained.