Cross-regulation between the Wnt and nuclear factor (NF)-κB signaling pathways has emerged as an important area for the regulation of a diverse array of genes and pathways active in chronic inflammation, immunity, development, and tumorigenesis. The ligands, kinases, transcription factors, and products of their target gene expression are involved in cross-regulation of these two signaling pathways. Both β-catenin and NF-κB activate inducible nitric oxide synthase (iNOS) gene expression; however, β-catenin also exerts an inhibitory effect on NF-κB-mediated transcriptional activation, including iNOS. The recent discovery of functional cross-regulation between these two pathways has shown complex roles for Wnt/β-catenin and NF-κB signaling in the pathogenesis of certain cancers and other diseases. This review focuses on the molecular mechanisms of cross-regulation between Wnt/β-catenin and NF-κB signaling pathways in cancer cells.