Abstract: Markers on chromosome 2 are associated with cancer predisposition, as shown by linkage analysis, in a significant fraction of families with a history of colon and other cancers. Tumors from these patients progressed through the same series of accumulated mutations in oncogenes and tumor suppressor genes found in non-familial cases, but showed no losses of heterozygosity for the linked chromosome 2 markers. DNA from the tumors (but not normal tissues) in most familial cases revealed a consistent and distinct abnormality: rearrangements in short repeated sequences throughout their genomes. This abnormality suggests that a large number of replication errors had occurred during tumor development. Methods are presented for detecting the presence of the gene which predisposes people to have colon and other tumors and for utilizing this information for diagnostic, prognostic, and preventive purposes. DNA markers useful for such methods are also described.