Abstract: Single Nucleotide Polymorphism (SNP) represents a variation in sequence (polymorphism) between individuals caused by a change in a single nucleotide. This process is responsible for most of the genetic variation between individuals. Furthermore, the identification of distinct SNPs may play a crucial role in assessing a potential genetic influence for those disorders that do not appear to have a simple genetic transmission. In turn, the identification of genetic risk factors may contribute to determine biological markers of disease that can be used for the preclinical diagnosis of a pathological condition. Early diagnosis is important for enacting successful therapeutic strategies. In order to obtain more informative data, multiple SNPs should be tested simultaneously in the same individuals. A common protocol used in SNPs investigations is based on Single Base Extension (SBE) followed by microarrays hybridization, in which each DNA sample is hybridized on two arrays: one used to explore the existence of “A” and “T” in the SNP locus, the other array for “C” and “T”. To obtain a global evaluation of the frequency with which each SNP is represented in the population, it is necessary to make a quantitative comparison of the signals recorded from the two arrays. Because of many technical reasons, during this step a large quantity of noise is introduced, thus compromising the reliability of the final data. Here we present a simple approach, based on the usage of three arrays instead of only two, which can address this problem. We also give a statistics method for data processing to be used with the proposed experimental protocol.