Notch receptor signaling has very distinctive roles in cancers originating from different types of cells that reflect its complex functions in normal tissue development and homeostasis. For example, recent studies have shown that Notch signals are oncogenic in pre-T cells but suppress tumor development in keratinocytes. Notch signaling contributes to pre-malignant metaplastic changes that precede pancreatic carcinoma, and it is also likely to be involved in other forms of metaplasia. In addition, several viral oncoproteins and chromosomal translocations target one or more components of a Notch transcriptional activation complex.