This genetic study provides evidence that the three major CARD15/NOD2 variant alleles and the CD14 –159C/T polymorphism are associated with Crohn’s disease (CD) susceptibility in the Saudi population; however, there is no evidence that the TLR4 (Thr399Il) or CARD15/NOD2 polymorphisms can be considered risk factors for Crohn’s disease. Here, NOD2 is linked to Cowden disease.