Aberrant methylation of the cyclin-dependent kinase inhibitor genes p15 (CDKN2B or p15INK4b) and p16 (CDKN2A or p16INK4a) on chromosome 9p21 in the peripheral circulation of HCC patients using MSP is one of first detected epigenetic changes associated with hepatocellular tumorigenesis. The gene discussed is CDKN2B; the disease is hepatocellular carcinoma.