Beta-TrCP is a component of the ubiquitin ligase complex targeting β-catenin for proteasomal degradation, and is a negative regulator of Wnt/β-catenin signaling. To determine whether genetic alterations of the β-TrCP gene are involved in the development or progression of gastric cancer, we analyzed its somatic mutations in 95 gastric cancers by single-strand conformational polymorphism and sequencing. We found five missense mutations (5.3%): A99V, H342Y, H425Y, C206Y, and G260E. Tissue carrying mutations showed moderate to strong cytoplasmic and/or nuclear staining of β-catenin by immunohistochemistry. Thus, somatic mutations of the β-TrCP gene may contribute to the development of gastric cancer through β-catenin stabilization.