Background: Epigenetic regulation of gene expression is a common feature of cancer development and progression. The search for new biomarkers and tools to detect cancer in its early stages has unveiled the usefulness of epigenetics and genes epigenetically regulated as potential targets. Among them, genes encoding mucins have been shown to be regulated by DNA methylation and histone modifications in epithelial cancer cells. These genes encode either secreted glycoproteins necessary for epithelial homeostasis or membrane-bound glycoproteins that participate in tumor progression. Objective: The important biological functions played by these large molecules in pathophysiology of the epithelia make them key genes to target to propose new therapeutic strategies and new diagnostic and/or prognostic tools in cancer. Results: In that context, the recent data regarding the epi-genetic regulation of these genes are reported and their potential as bio-markers in cancer is discussed. Mucin genes are also potentially interesting to study as they may be regulated by miRNAs but also regulate miRNA activity. Conclusion: Epigenetic regulation of mucin genes is at its dawn, but there is great potential in that research to (with new technologies and high-throughput methods) provide quickly new biomarkers (diagnostic and/or prognostic), help tumor identification/classification and propose new therapeutic targets to the clinician and pathologist.