It is currently believed that normal genes, presumably in the class of tissue differentiation genes (proto-oncogenes), are responsible for the malignant transformation of human cells. As such, they cannot be appropriately used to identify individuals at risk for cancer. Based on our experience with a cell system from patients with adenomatosis of the colon and rectum (ACR), we suggest that predisposition to cancer can best be detected as a global syndrome at the phenotypic level. The ability to distinguish a cancer predisposed person from a normal individual in well-defined populations should qualify a test as "cancer specific". An underlying assumption in these studies is that predisposition to cancer, in general, is associated with an autosomal dominant trait in obligatory heterozygote gene carriers.