NOD1/CARD4 and NOD2/CARD15 are members of Nod-like receptor family. They are located in cytosol, bind bacterial and viral ligands and play a key role in realization of innate and adaptive immune response, apoptosis, autophagy, and reactive oxygen species generation. Polymorphisms in NOD1/CARD4 and NOD2/CARD15 genes may shift balance between pro- and anti-inflammatory cytokines, modulating the risk of infection, chronic inflammation and cancer. NOD1/CARD4 and NOD2/CARD15 gene polymorphisms may be associated with altered risk of gastric, colorectal, breast, ovarian, prostate, testicular, lung, laryngeal, liver, gallbladder, biliary tract, pancreatic, small bowel, kidney, urinary bladder cancer, skin cancer, nonthyroid endocrine tumors, lymphoma and leukemia. The short list of such polymorphisms perspective for oncogenomic investigations may include rs2006847, rs2066845, rs2066844, rs2066842, ND(1)+32656, rs2075820 whereas rs104895493, rs104895476, rs104895475, rs104895474, rs104895473, rs104895472, rs104895462, rs104895461, rs104895460, rs104895438, rs5743291, rs5743260, rs2076756, rs2066843, Pro371Thr, Ala794Pro, Gln908His, rs72551113, rs72551107, rs6958571, rs2907749, rs2907748, rs2075822, rs2075819, rs2075818 may be added to the extended list. Reasons of discrepancies between different studies include confounding host genetic, bacterial, or environmental factors modulating penetrance of variant allele and affecting risk of condition increasing cancer risk, different bacterial impact in aetiology of such conditions, differences in sample size, clinicopathological characteristics, diagnostics, stratification, genotyping methods, and chance.