We provide a comprehensive description of our microarray-based technique for the simultaneous detection of multiple CpG islands in cancer. Amplicons from tumor and control samples were pools of differentially methylated CpG island fragments hybridized to a panel of approximately 8000 CpG island tags. Data analysis identified 694 CpG island loci hypermethylated in a group of 14 colorectal tumors. The Stanford hierarchical cluster algorithm segregated the tumors into two subgroups, one of which exhibited a high level of concurrent hypermethylation while the other had little or no methylation. This is in agreement with previous observations of a CpG island methylation phenotype present in colorectal tumors. The present study demonstrates that this microarray-based technique is useful in classifying tumors according to their methylation profiles.