Both genetics and epigenetics regulate gene expression in cancer. Regulation by genetics involves a change in the DNA sequence, whereas epigenetic regulation involves alteration in chromatin structure and methylation of the promoter region. During the initiation, development, and progression of cancer, a number of genes undergo epigenetic changes. Some of these changes can be used as biomarkers for early detection of cancer as well as to follow treatment. A panel of epigenetic biomarkers is preferred to a single biomarker in clinical assays. Changes in gene expression due to epigenetic regulation can be reversed by chemicals, and this approach opens up a novel approach in cancer prevention and treatment.