Approximately 13% of colorectal cancers display microsatellite instability (MSI), a form of replication error repair. Colorectal cancers developing in individuals with constitutional defects in the mismatch repair (MMR) genes hMLH1, hMSH2, hPMS1 and hPMS2 consistently show evidence of this phenomenon. Since MSI is indicative of MMR deficiency, testing colorectal cancers for MSI provides a method of refining the identification of carriers of germline MMR mutations. To assess which microsatellites represent the best reporters of replication error (RER) status we have examined 116 early onset colorectal cancers for MSI. MSI was assessed using eight dinucleotide- and two mononucleotide-repeat fluorescently labelled polymerase chain reaction (PCR) markers. The two mononucleotide repeat markers (BAT25 and BAT26) were highly sensitive and typing of either represents an efficient strategy for defining RER status of colorectal cancers and obviates the requirement of typing numerous microsatellite markers.