Replication error (RER) is defined as mutation events in repetitive DNA segments. To investigate further the RER phenomenon and reveal any differences in mutation outcome between different short tandem repeat (STR) loci, we have investigated the somatic mutation rate and the size distribution of new tumour alleles in four tetranucleotide STRs in a large material of unselected colorectal adenocarcinomas. DNA was extracted from the blood and carcinomas of 217 patients. All blood/tumour pairs were analysed using the STRs HUMTHO1, HUMFES/FPS, HUMVWA31/A and HUMF13A1. Mutations are detected at all four loci. There are substantial differences in mutation rate and mutation direction (i.e. expansion versus contraction) between different STR loci. In all four STRs, the majority of events represent gain or loss of a single repeat. Almost all new tumour alleles correspond to known alleles in a population database, indicating that these are also composed of integers of the four base pair repeat. There is no statistically significant size bias in the mutating alleles as compared to the allelic distribution in the population database.