The comprehensive identification of NF-κB mutations in distinct lymphoma subtypes together with new insights from the mechanistic dissection of NF-κB pathway activation in the normal cellular counterparts of these tumours, i.e., GC and post-GC B cells, are beginning to establish a framework that may be exploited for the development of effective, more specific NF-κB inhibitors lacking systemic side effects. This evidence concerns the gene NFKB1 and lymphoma.