The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is an evolutionarily conserved multi-protein complex found in plants and animals that regulates pivotal cellular processes such as the cell cycle and apoptosis, as well as a number of oncogenic signal transduction pathways. Cancer diseases still belong to the most challenging human diseases that are associated with high mortality rates and that are difficult to cure with still only limited knowledge about the mechanisms of their development. The CSN is a potential key player in tumorigenesis and its subunits are often overexpressed in tumors and because the CSN is involved in the regulation of a number of processes that are relevant to carcinogenesis and cancer progression, e.g. cell cycle control, signal transduction, and apoptosis. Beyond the altered expression of the CSN and its subunits in tumors, the CSN has an established impact on several important cellular functions that often are dysregulated in tumorigenesis.