It is increasingly apparent that cancer development not only depends on genetic alterations but on an abnormal cellular memory, or epigenetic changes, which convey heritable gene expression patterns critical for neoplastic initiation and progression. These aberrant epigenetic mechanisms are manifest in both global changes in chromatin packaging and in localized gene promoter changes that influence the transcription of genes important to the cancer process. An exciting emerging theme is that an understanding of stem cell chromatin control of gene expression, including relationships between histone modifications and DNA methylation, may hold a key to understanding the origins of cancer epigenetic changes. This possibility, coupled with the reversible nature of epigenetics, has enormous significance for the prevention and control of cancer.