Mutational processes occur in normal tissues from conception throughout life. Field cancerization describes the preconditioning of an area of epithelium to tumor growth. Pre-invasive lesions may arise in these fields, however only a minority of pre-invasive neoplasia progresses to overt malignancy. Within this review we discuss recent advances in our understanding of genomic instability processes in normal tissue, describe evolutionary dynamics in pre-invasive disease and highlight current evidence describing how increasing genomic instability may drive the transition from pre-invasive to invasive disease. Appreciation of the evolutionary rulebooks that operate in pre-invasive neoplasia may facilitate screening strategies, risk-stratification of pre-invasive lesions and precipitate novel preventative treatments in at-risk patient populations.