To confirm the beneficial effects of endothelial Dll4 overexpression in an autochthonous tumor model, and to gain a more thorough insight into the morphological, functional and molecular consequences of increased Dll4/Notch signaling, skin tumorigenesis was initiated in D4BE and D4OE mice (n = 10) by a single topical DMBA treatment and then promoted by topical TPA applications twice per week for 19 weeks. This evidence concerns the gene DLL4 and neoplasm.