Mucins are high molecular weight glycoproteins that play important roles in diagnostic and prognostic prediction and in carcinogenesis and tumor invasion. Regulation of expression of mucin genes has been studied extensively, and signaling pathways, transcriptional regulators, and epigenetic modification in promoter regions have been described. Detection of the epigenetic status of cancer-related mucin genes is important for early diagnosis of cancer and for monitoring of tumor behavior and response to targeted therapy. Effects of micro-RNAs on mucin gene expression have also started to emerge. In this review, we discuss the current views on epigenetic mechanisms of regulation of mucin genes (MUC1, MUC2, MUC3A, MUC4, MUC5AC, MUC5B, MUC6, MUC16, and MUC17) and the possible clinical applications of this epigenetic information.