It is now apparent that epigenetic abnormalities, in particular altered DNA methylation, play a crucial role in the development and progression of human cancers. DNA hypermethylation at promoter CpG islands is now recognized as a third mechanism by which inactivation of tumor suppressor genes occurs. Aberrant CpG island hypermethylation is also frequently observed in chronic inflammation and precancerous lesions, which suggests that it is an early event in tumorigenesis that could serve as a useful tumor marker. A variety of screening techniques have been developed for genome-wide screening of methylation status. Of those, transcriptome analysis coupled with pharmacological unmasking has emerged as a powerful tool for revealing DNA methylation patterns in cancer cells and identifying new tumor marker candidates.