To study the genetic diversity of Sao Miguel's population we compared 21 microsatellite loci in 204 individuals from Sao Miguel island and 103 individuals from mainland Portugal. The results show that Sao Miguel and mainland Portugal populations have an average gene diversity of 0.767 and 0.765, respectively. Allele frequencies of all markers are comparable to other European populations. This observation is corroborated by the genetic relationships analysis based on the NJ tree and principal component, where Sao Miguel is closely related to mainland Portugal. Overall, the data suggests that Sao Miguel does not show population structure and is outbred with high genetic diversity. Moreover, the characterization here described is crucial to predict and explain genotypes implicated in genetic diseases in the Azorean population. Am. J. Hum. Biol., 2008. © 2007 Wiley-Liss, Inc.