The fifth base in human DNA, 5-methylcytosine, is inherently mutagenic. This has led to marked changes in the distribution of the CpG methyl acceptor site and an 80% depletion in its frequency of occurrence in vertebrate DNA. The coding regions of many genes contain CpGs which are methylated in sperm and serve as hot spots for mutation in human genetic diseases. Fully 30-40% of all human germline point mutations are thought to be methylation induced even though the CpG dinucleotide is under-represented and efficient cellular repair systems exist. Importantly, tumor suppressor genes such as p53 also contain methylated CpGs and these serve as hot spots for mutations in some, but not all, human cancers. Comparison of the spectrum of mutations present in this gene in different human cancers allows for predictions to be made on the molecular mechanisms of tumorigenesis.