The cytoplasmic b-catenin protein is implicated as a cell-cell adhesion regulator coupled with cadherin and is considered as a member in the wingless/Wnt signal transduction pathway. Mutations in CTNNB1, the gene encoding b-catenin, tend to impact or even eliminate APC-dependent serine and threonine phosphorylation sites in exon 3, resulting in oncogenic stabilization of the protein. Mutations in the b-catenin gene are uncommon in NSCLC occurring in about 1-4% of the cases. CTNNB1 S37C is a gain of function mutation, has been described in 0.3% of non-small cell lung carcinomas and is likely oncogenic. However, its prognostic and therapeutic significance remains to be fully elucidated.