Single Nucleotide Polymorphisms (SNPs) are believed to contribute strongly to the genetic variability in living beings, and SNP and mutation discovery are of great interest in todays Life Sciences. A comparatively new method to discover such polymorphisms is based on base-specific cleavage, where resulting cleavage products are analyzed by mass spectrometry (MS). One particular advantage of this method is the possibility of multiplexing the biochemical reactions, i.e. examining multiple genomic regions in parallel. Simulations can help estimating the performance of a method for polymorphism discovery, and allow us to evaluate the influence of method parameters on the discovery rate, and also to investigate whether the method is well suited for a certain genomic region.