As one of the cyclin-dependent kinase inhibitors that inhibit cyclin-dependent kinases (CDK) 4 and 6, p16INK4a is encoded by the tumor suppressor gene CDKN2A. It is a specific inhibitor of cdk4/cdk6, and a tumor suppressor involved in the pathogenesis of a variety of malignancies. Recent analyses of the p16INK4a gene revealed homozygous deletions, nonsense, missense, or frameshift mutations in several human cancers. Although the frequency of p16INK4a abnormalities is higher in tumor-derived cell lines than in unselected primary tumors, significant subsets of clinical cases with aberrant p16INK4a gene have been reported among melanomas, gliomas, esophageal, pancreatic, lung, and urinary bladder carcinomas, and some types of leukemia.