Epigenetics plays an important role in tissue differentiation and phenotypic changes are associated with extensive modifications in epigenetic patterns such as DNA methylation (DNAme), histone methylation and acetylation marks, and micro RNAs. From a diagnostic perspective, DNAme is one of the more tractable epigenetic changes; differentially affecting a large number of genes. Variations can be measured accurately, on any given set of CG sites, by sequencing bisulfite converted DNA. The promise of DNAme is that biomarkers can be found in every kind of gene from rare unstable cell-cycle enzymes to highly expressed structural proteins. Almost any kind of biological specimen is amenable and the changes can be measured in tissue biopsies, scrapes, aspirates, urine, blood and other fluids. To date, hundreds of differentially methylated genes have been identified in cancer that can potentially function as biomarkers. The most common kind of change, studied, is CpG island methylation of tumor suppressor genes that modifies transcription. Despite a great many candidates, few of the DNAme markers have been adequately validated for routine clinical use. Important current limitations of epigenetic biomarkers are that assays are diverse; gene lists are large; comparative data are few, and disagreements in published papers are frequent.