To gain a better understanding of tumor angiogenesis, new techniques forisolating endothelial cells (ECs) and evaluating gene expression patterns weredeveloped. When transcripts from ECs derived from normal and malignantcolorectal tissues were compared with transcripts from non-endothelial cells,over 170 genes predominantly expressed in the endothelium were identified.Comparison between normal- and tumor-derived endothelium revealed 79differentially expressed genes, including 46 that were specifically elevatedin tumor-associated endothelium. Experiments with representative genes fromthis group demonstrated that most were similarly expressed in the endotheliumof primary lung, breast, brain, and pancreatic cancers as well as inmetastatic lesions of the liver. These results demonstrate that neoplastic andnormal endothelium in humans are distinct at the molecular level, and havesignificant implications for the development of anti-angiogenic therapies inthe future.