The molecular events associated with the development of adenocarcinoma of the oesophagus are not well understood. Gene expression associated with oesophageal adenocarcinoma was investigated using a cDNA array containing 1,176 human cancer-associated genes. Approximately 59% of the genes were expressed at detectable levels with 15 genes (1.3%) exhibiting differential (> 2.5-fold) expression in either normal oesophagus or adenocarcinoma tissue. Nine genes were up-regulated in oesophageal adenocarcinoma tissue (matrix metalloproteinase 11 (MMP11), ornithine decarboxylase (ODC), cytokeratins 8 and 18, integrin alpha 3 (ITGA3), integrin alpha 6 (ITGA6), BIGH3 (transforming growth factor beta-induced), beta-catenin and CDC25B (M-phase inducer phosphatase 2)). Six genes were down-regulated in adenocarcinoma tissue (cytokeratin 4, plasminogen activator inhibitor 2 (PAI-2), interleukin 1 receptor antagonist (IRAP), cytokeratin 13/15/17, MAD and retinoic acid receptor gamma 1 (RARG)). Many of these differentially expressed genes influence cell-cell adhesion, cell-extracellular matrix and composition, transcriptional activation and cell cycle progression and are likely to contribute to development of oesophageal adenocarcinoma.