Gastrointestinal cancers account for approximately 25% of all cancer deaths in the Western world. There is a need for a preventive strategy that can utilize biomarkers in order to stratify patients into appropriate screening or surveillance programs. Biomarkers are clinical variables associated with clinical outcomes. In cancer biology, the best biomarkers are germline adenomatous polyposis coli mutations, which are highly predictive of colon cancer. In other areas, such as Barrett's esophagus, despite early excellent success in identifying the importance of p16, p53, and aneuploidy in esophageal adenocarcinoma pathogenesis, useful biomarkers are still not widely used in clinical practice. New molecular biomarkers may be identified in the next decade, such as epigenetic methylation patterns and genetic polymorphisms. In the meantime, clinicians must rely on robust, inexpensive methods such as standard histopathology. Dysplasia is still the mainstay of cancer prediction in most inflammatory disorders of the GI tract and is an independent marker of cancer risk.