We have isolated a candidate tumor suppressor gene from a 600-kb region on chromosome 8p21.3-p22 that is commonly deleted in sporadic hepatocellular carcinomas (HCC), colorectal cancers (CRC), and non- small cell lung cancers (NSCLC). As this gene encodes a protein of 375 amino acids that bears significant sequence similarity to the extracellular (ligand-binding domain of platelet-derived growth factor receptor beta, we have designated it PRLTS (PDGF-receptor beta-like tumor suppressor). Structural rearrangement involving this gene was found in a sporadic NSCLC. In addition, somatic missense and frame- shift mutations were found in two HCCs and one CRC. These findings indicate that inactivation of the PRLTS gene may play a significant role in development of some carcinomas.