A unique feature of isolated cultured endothelial cells is their ability, in vitro, to differentiate into an interconnected network of tube-like structures when exposed to a suitable extracellular matrix and combination of growth factors or other stimuli. In the present study we have used the AffymetrixTM oligonucleotide array technology to identify common genes whose expression is upregulated in endothelial cells differentiating into tube-like structures in three different in vitro models. In addition, we also compared the genes expressed in these models to a fourth model in which endothelial cells were exposed to one of the growth factor combinations in 2D cultures; in the 2D cultures the cells do not differentiate into tube-like structures. We reasoned that these comparisons would allow the identification of a common set of genes used by endothelial cells to migrate, elongate, invade matrix, form new intercellular junctions, and to form lumens. Finally, the expression of rat homologues of certain of the genes of interest were confirmed in an in vivo model of angiogenesis.