Cell-cell adhesion is a fundamental activity to allow the maintenance of epithelial integrity, and defects impairing this process promote the formation of tumors such as colorectal cancer (CRC). In this regard, a crucial role is played by adhesion molecules, named cadherins, which exert their function through the inhibition of the β-catenin signaling proliferation pathway, constitutively activated in CRC. A number of reports, published over the last decade, have highlighted the existence of a novel cadherin family member, called μ-protocadherin, to underline the hybrid nature of its extra-cellular region, including both cadherin-like and mucin-like domains. Is has been shown that this protein plays an important role in inter-cellular adhesion processes, inhibits β-catenin activity in normal colorectal mucosa, undergoes a down-regulated expression in CRC and is up-regulated upon treatment with chemoprevention agents against this tumor.