Genetic instability has long been hypothesized to be a cardinal feature of
cancer. Recent work has strengthened the proposal that mutational alteratio
ns conferring instability occur early during tumour formation. The ensuing
genetic instability drives tumour progression by generating mutations in on
cogenes and tumour-suppressor genes. These mutant genes provide cancer cell
s with a selective growth advantage, thereby Leading to the clonal outgrowt
h of a tumour. Here, we discuss the role of genetic instability in tumour f
ormation and outline future work necessary to substantiate the genetic inst
ability hypothesis.