Epigenetic modifications, particularly DNA methylation, is commonplace and a remarkable factor in carcinogenesis transformation. Conspicuously, previous findings have presented a cluster of irregular promoter methylation alterations related with silencing of tumor suppressor genes, little is accepted regarding their sequential DNA methylation (hypo and hyper) modifications during the cancer progression. In this way, fluctuations of DNA methylation of many genes, especially MYC, SMAD2/3, and DNMT3A, have an impressive central key role in many different cancers, including colorectal cancer (CRC). CRC is distinguished by DNA methylation, which is related to tumorigenesis and also genomic instability. Importantly, molecular heterogeneity between multiple adenomas in different patients with CRC may show diverse developmental phenotypes for these kinds of tumors. Conclusively, studying factors that are involved in CRC carcinogenesis, especially the alterations in epigenetic elements, such as DNA methylation besides RNA remodeling, and histone modification, acetylation and phosphorylation, can be influential to find new therapeutic and diagnostic biomarkers in this type of malignancy. In this account, we discuss and address the potential significant methylated modifications of these genes and their importance during the development of CRC carcinogenesis.