Epigenetic dysregulation is a common feature across all cancer types. Epigenetic mechanisms, from DNA methylation to histone modifications, allow for a vast number of cellular phenotypes to be created from the same genetic material. Just as certain genetic changes play a key role in tumor initiation and progression, epigenetic changes may also set the course of tumor development and be required for malignant transformation. The most frequently studied epigenetic changes investigated thus far are global genomic DNA hypomethylation along with specific hypermethylation, predominantly at promoter CpG islands of tumor suppressor genes. In addition to DNA methylation changes at CpG islands, there is an abundance of other epigenetic alterations occurring within cancer cells including DNA methylation alterations outside of CpG islands, non-CpG methylation, changes in cytosine oxidative species (hydroxymethylcytosine, formylcytosine, carboxylcytosine) levels, and histone modifications. This chapter examines epigenetic alterations beyond the island, and summarizes recent findings in DNA-based epigenetic regulation of the two most commonly diagnosed cancers in the Western world: colorectal cancer and prostate cancer.