Viral infected, tumor-transformed or allogeneic “non-self” cells down-regulate, lack or express different HLA-I alleles, thus boosting the NK cell-mediated killing of these dangerous targets via the engagement of aNKRs, that includes Natural Cytotoxicity Receptors (NCRs) (NKp30, NKp46, and NKp44), C-type lectin receptors (NKG2C, NKG2D), DNAM-1 and activating KIRs (aKIRs) (“missing self hypothesis”) (6, 12–14). This evidence concerns the gene KLRK1 and neoplasm.