More than 20 years ago, several groups identified CARD8 as a 48 kDa protein, also termed CARD-inhibitor of NF-kappa-B-activating ligand (CARDINAL) or tumor-up-regulated CARD-containing antagonist of caspase 9 (TUCAN) (Figure 1) [53,54,55]. This evidence concerns the gene CARD8 and neoplasm.