Human cancers harbour numerous mutations and it has been proposed that these result from some form of inherent genomic instability. Some cancers have proven genomic instability or features that are indicative of this. Inherited cancer syndromes exist that are caused by deficient DNA repair or chromosomal integrity. By contrast, theoretical analysis and experimental data from sporadic colorectal tumours provide little general evidence of genomic instability in early lesions. These apparently conflicting data raise the question of whether or not genomic instability is necessary for driving tumour growth, and whether or not it is the usual initiating event in tumorigenesis.