Aberrant DNA methylation is common in cancer. DNA methylation profiles differ between tumor types and subtypes and provide a powerful diagnostic tool for identifying clusters of samples and/or genes. DNA methylation data obtained with the quantitative, highly sensitive MethyLight technology is not normally distributed, it frequently contains an excess of zeros. Established tools to analyze this type of data do not exist. Here, we evaluate a variety of methods for cluster analysis to determine which is most reliable.