Instability of repetitive DNA sequences causes numerous hereditary disorders in humans, the majority of which are associated with trinucleotide repeat expansions. Here, we describe a unique system to study instability of triplet repeats in a yeast experimental setting. Using fluctuation assay and the novel program FluCalc we are able to accurately estimate the rates of large-scale expansions, as well as repeat-mediated mutagenesis and gross chromosomal rearrangements for different repeat sequences.