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Aberrant Wnt/β-catenin signaling has often been reported in different cancers, particularly colorectal cancer (CRC), and this signaling cascade is central to carcinogenesis. Approximately 80% of CRC cases harbor mutations in the adenomatous polyposis coli gene, and half of the remaining cases feature mutations in the β-catenin gene that affect the Wnt/β-catenin signaling pathway. Unsurprisingly, the Wnt/β-catenin signaling pathway has potential value as a therapeutic target in the treatment of CRC. Several inhibitors of the Wnt/β-catenin signaling pathway have been developed for CRC treatment, but so far no molecular therapeutic targeting this pathway has been incorporated into oncological practice. In this review, we discuss the role of Wnt/β-catenin signaling in CRC and its potential as a target of innovative therapeutic approaches for CRC.