Cancer is by and large caused by a combination of genetic lesions and obstructed gene expression patterns that put afflicted cells in a growth advantage. Recent research has shown that DNA methylation, histone modifications, chromatin remodeling, and noncoding RNA have profound influence on tumorigenesis. The epigenetic modifications act in concert, sometimes antagonistically, and manage to orchestrate the gene expression pattern by making the DNA more or less accessible to transcription factors or other DNA-binding proteins. Here, we review the components directly influencing chromatin structure in normal cells and parallel that with the ones that have been implicated in driving or initiating tumorigenesis. The processes leading to pluripotency from a terminally differentiated state show similarities in the pathogenesis of neoplasia, and we highlight some of the recent findings that epigenetic patterning or remodeling is instrumental in the formation of cancer stem cells and tumor-initiating cells.