An insertion mutation at nucleotide 3020 (3020insC) in the CARD15 gene, originally reported as NOD2, has been strongly associated with Crohn's disease. The CARD15 G2722C missense mutation was also shown to be associated with this disease. We studied 130 Dutch Crohn's disease patients, with a median follow up of 9.2 years, in relation to the Vienna classification, and 152 ethnically matched healthy controls. We confirm reports that the CARD15 3020insC mutation increases the susceptibility to Crohn's disease, but we do not confirm this relationship for CARD15 G2722C. Our findings suggest that these mutations are not a marker of a particular form of Crohn's disease according to the Vienna classification. Whether the CARD153020insC and CARD15 G2722C mutations are responsible for a different etiopathogenic mechanism in a subgroup of patients remains to be studied.