NF-κB pathway exerts an essential function in the regulation of the immune response, which has been the nucleus of numerous studies for the past 25 years. Both activation of the pathway and termination of the NF-κB response are tightly regulated events, which is essential to prevent exacerbated inflammatory responses. Thus, alterations in NF-κB regulatory elements might result in tissue damage and cancer in different systems. In addition, several of the proteins involved in NF-κB regulation display additional, and much less studied, functions that connect with specific NF-κB-unrelated pathways. Many of these pathways are in turn regulators of particular physiologic and/or pathologic responses. Which are the principal non-conventional functions that have been identified for specific NF-κB elements, how they connect with other signaling pathways and what is their potential impact on cancer is the focus of this review.