Small insertions or deletions of nucleotides are common polymorphic variations in the human genome and can result in a predisposition to disease. However, high throughput methods for detecting these variations are limited. This report describes a method to detect this variation based on sequencing the boundaries of nucleotide alterations using the Pyrosequencing technique. This method can optimally detect up to 100 base pair nucleotide insertions and deletions, and also complicated genomic rearrangements.