Adenocarcinomas of the distal esophagus mainly develop from intestinal metaplasia (Barrett's esophagus) through intermediate steps of low-grade and high-grade intraepithelial neoplasia. Histopathological examination of endoscopic biopsies constitutes the gold standard for estimating the cancer risk of a patient with Barrett's esophagus. Several prospective biomarker phase IV studies have demonstrated the predictive value of e.g. allelic loss of TP53, tetraploidy and aneuploidy as well as cyclin D1 expression. Among the relevant biomarkers from retrospective phase III studies are polysomy and specific DNA gains and losses, markers of proliferation (Mib-1) and methylation markers. As there are conflicting results in the literature and these analyses are costly, their use in routine patient care cannot yet be recommended. However, immunostaining for several markers may assist in the classification of intraepithelial neoplasia in individual difficult cases.