The emerging relevance of colorectal cancer (CRC) in the last few years is well known. In Spain, this is the most prevalent malignancy and the second cause of can- cer-related mortality. Focusing on both genders, over 25,000 new cases are diagnosed in Spain, and around 13,000 individuals die from this condition every year (1). Thus, more than ever, this unquestionable significance makes our deeper understanding mandatory, which has evolved on an ongoing basis ever since Fearon and Vogelstein defined their colorectal carcinogenesis model back in 1990 (2). Today, the hypothesis that most CRCs emerge from adenomas via the suppressor –also referred to as chro- mosome instability (CI)– route, which is initiated by a mutation in gene APC –this is the classical description of colorectal carcinogenesis corresponding to the adenoma- carcinoma sequence (2)–, is only met by 60% of cases (3), and two additional alter- native, non –excluding routes, are now considered– the microsatellite instability (MSI) pathway, associated with Lynch syndrome and a small proportion of sporadic cases, and the methylator phenotype pathway, most recently identified and referred to as CIMP (CpG Island Methylator Phenotype) in the English-language literature. Advances occurred in the understanding of the molecular basis of CRC are doubtless the strongest drive towards a more rational, specific management for this condition via the identi- fication of new, more specific therapy targets, as well as markers to describe the various behaviors of the disease. Epigenetics is a term used to describe the mechanisms than may modify at various levels the expression of specific genes without altering the corresponding DNA sequence, including DNA methylation, chromatin remodeling, and other processes mediated by non-coding RNA molecules (4). From a general perspective, a tumor would originate from multiple, cumulative changes in the genome of its cells, both epigenetic and DNA sequence changes. These sequence changes include deletions in chromosome regions with gene loss that may be associated with negative cell- cycle regulation (tumor suppressor genes), mutations that may activate or inactivate a number of proteins, gene amplifications entailing an overexpression of specific genes, and even loss or gain of entire chromosomes. As mentioned above, colorectal carcinogenesis pathways are sometimes mutually excluding, as is the case with MSI and CI, whereas on other occasions there may be some overlap, as occurs with CIMP. CRC is being increasingly classified into various phenotypes according to its molecular profiles (5). Thus, its classification from a molecular viewpoint is based on the predominant cell event (CI, MSI, CIMP) or, equivalently, according to the event-initiating factor (suppressor pathway for CI; mutation pathway for MSI; methylator pathway for CIMP). CIMP relates to changes at the epigenetic level, more specifically at the DNA methylation level. CpG islands are DNA regions that conform around 40% of gene Methylation in colorectal cancer 61130-0108/2012/104/3/107-110 REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS Copyright © 2012 ARÁN EDICIONES, S. L. REV ESP ENFERM DIG (Madrid) Vol. 104, N.° 3, pp. 107-110, 2012 E d i t o r i a l