Abstract Galectin-3 (gal-3), a member of the β-galactoside–binding proteins family, was identified as a binding partner of β-catenin. Analysis of the human gal-3 sequence reveled a structural similarity to β-catenin as it also contains the consensus sequence (S92XXXS96) for glycogen synthase kinase-3β (GSK-3β) phosphorylation and can serve as its substrate. In addition, Axin, a regulator protein of Wnt that complexes with β-catenin, also binds gal-3 using the same sequence motif identified here by a deletion mutant analysis. The data presented here give credence to the suggestion that gal-3 is a key regulator in the Wnt/β-catenin signaling pathway and highlight the functional similarities between gal-3 and β-catenin.