Aberrant DNA methylation is one of the major characteristics of tumor cells in addition to genetic and other epigenetic alterations. Evidence shows that both regional hypermethylation and global hypomethylation can occur in cancer cells. Increased DNA methylation can be found at select tumor-suppressor gene promoters, causing the silencing of these genes in tumorigenic cells. At the same time, a global decrease in DNA methylation is frequently observed in cancer cells, which may contribute to genome instability. Unlike genetic mutations, hypermethylation at tumor-suppressor gene promoters can be reversed with epigenetic therapy by using DNA demethylating agents. To better understand the mechanisms of cancer initiation and progression, and to better assess the effects of epigenetic therapy, a reliable high-throughput method for genome-wide DNA methylation analysis is needed. Recently, the process of coupling methylated DNA immunoprecipitation (mDIP) with microarray hybridization has been proven to be a successful strategy to map genome-wide DNA methylation patterns in different cell types.