Barrett's esophagus (BE) is a preneoplastic condition that predisposes to esophageal adenocarcinoma. Although data on the occurrence of BE in children are limited, recent studies have suggested an increase in the pediatric population. BE is thought to be a complex disease in which individual genetic predisposition interacts with environmental stimuli. Early premalignant clones produce biological and genetic heterogeneity, resulting in stepwise changes in differentiation, proliferation, and apoptosis, allowing disease progression under selective pressure. The value of endoscopic surveillance biopsy for dysplasia and carcinoma in patients with BE is controversial. Thus, the recognition of early and objective alternative risk markers, less susceptible of sampling error, will be of relevance in the management of BE patients. The possibility of performing molecular genetics on paraffin-embedded biopsies will expand our understanding of the natural history of BE and may lead to the use of biomarkers to inform treatment strategies.