Deregulation of the Wnt signalling pathway is a key event in the development of a broad spectrum of human malignancies and mutations in beta-catenin (CTNNB1), a central component of the Wnt pathway, have been detected in 10-15% of Wilms tumors (nephroblastoma). Furthermore, nuclear immunoreactivity for beta-catenin has been described even in the absence of detectable beta-catenin mutations. This suggests that other components of the Wnt pathway may be involved in the pathogenesis of a subgroup of Wilms tumors. Chibby (C22ORF2) is a recently identified antagonistic component of the Wnt pathway that inhibits the transcriptional activity of beta-catenin. Our study addresses the question whether mutation or down-regulation of Chibby is involved in Wilms tumorigenesis. We analysed the expression of Chibby by real time RT-PCR in 142 Wilms tumors, but there was no significant expression difference in any group of tumors stratified according to clinical, histological and mutational criteria. Mutation analysis of a smaller cohort did not reveal any mutations of the coding sequence. We only detected a constitutive splice variant leading to the absence of exon 4 in all Wilms tumors as well as in normal tissues. In addition, we detected a frequent silent polymorphism in the Chibby exon 4 sequence (435T/C). These data strongly suggest that despite its attractive function as a modulator of beta-catenin activity, Chibby is not involved in Wilms tumorigenesis.