Barrett’s esophagus is a columnar metaplasia conferring an increased risk of adenocarcinoma development. Evidence suggests that this increased risk is due to field cancerization – the formation of histologically undistinguishable field of clonally derived, mutant cells within the Barrett’s segment. Field cancerization can occur prior to both dysplasia and invasive neoplasia and potentially provides a mechanism for the development of multifocal and metachronous tumors. In the gastrointestinal tract, mutant clones spread predominately by crypt fission; the same is likely to be true in Barrett’s lesions. Epithelial interactions in the form of cooperation or competition between epithelial clones, as well as with stromal cells, may further drive clone growth. Field cancerization is a clinically relevant phenomenon, knowledge of which could influence the size of resection margins to enhance prognosis after curative surgery, as well as provide a rationale for the development of effective biomarkers for neoplasia risk in Barrett’s esophagus. This may provide a foundation for streamlined surveillance programs to prevent the development of invasive tumors.