While NK cells are known to possess the ‘innate’ ability to kill tumor cell targets in a major histocompatibility complex (MHC)-unrestricted fashion, it is the expression of stress ligands, such as MHC class I chain-related protein A and B (MICA and MICB), and apoptosis-inducing receptors, such as Death receptor (DR) 5, that appear to drive CSC susceptibility to NK cell targeting and killing. This evidence concerns the gene HLA-C and neoplasm.