As a subfamily of the cadherin superfamily, protocadherins are cadherin-like cell adhesion proteins that contain up to seven extracellular domains and are predominantly expressed in the nervous system. Importantly, the adhesion mechanism of protocadherins is distinct from classic cadherins. Through inactivation or overexpression, several protocadherins have been implicated in a variety of cancers. Protocadherin-20 (PCDH20), also known as protocadherin-13, is a 924 amino acid protein containing 6 cadherin domains and potentially functioning as a calcium-dependent cell-adhesion protein. In non-small cell lung cancer cell lines, a homozygous loss of PCDH20 was identified through either deletion of one allele and methylation of the other or methylation of both alleles. Hypermethylation of PCDH20 is associated with worse prognosis and clinical outcome, suggesting that PCDH20 may function as a tumor suppressor.