Netrin receptor DCC (deleted colorectal careinoma) was originally identified as a putative tumor suppressor gene that is lost in more than 70% of colorectal cancers. The DCC protein is a type I transmembrane glycoprotein that belongs to the immunoglobulin (Ig) superfamily. It is found in axons of the central and peripheral nervous system and in differentiated cell types of the intestine. Native DCC is found in three isoforms. Two forms, a long and a short isoform, are produced from the same gene but have different initiation sites. The third isoform, produced by alternative splicing, is expressed only in embryonic tissue. Colorectal tumors that lost their capacity to differentiate into mucus producing cells uniformly lack DCC expression. Inactivation of DCC due to allelic deletion or point mutations may cause both lymphatic and hematogenous metastasis of esophageal squamous cell carcinomas.