Clam farmers worldwide face several challenges, including irregular seed supply and high mortalities due to pathogenic organisms such asPerkinsus olseni. In Europe, there is a high unmet consumer demand for native clam species such asRuditapes decussatus. The high market value ofR. decussatusmakes the culture of this species potentially more attractive than that culture of the alien speciesRuditapes philippinarum. Thus, there is a market opportunity in breeding and producingR. decussatusat an industrial scale. A selective breeding program to improveR. decussatusperformance will be carried out in Portugal; and the first critical step to develop such a breeding program is the establishment of a founder population. In this study, intra- and interpopulation genetic diversity was assessed using 13 microsatellite markers in eight natural beds located in Portugal, Spain and Italy. Also, allele and genotypic frequencies of each microsatellite locus were assessed discriminating between clams infected and non-infected byP. olseni. All locations showed similar values for several genetic diversity parameters. Analyses of population differentiation (F_ST, Bayesian clustering and AMOVAs) revealed five genetically differentiated regions: Rías Altas and Rías Baixas (NW Spain), North/Central Coast of Portugal, Gulf of Cadiz and Adriatic Sea. Significant differences in the allelic and genotypic frequency distribution between infected clams and non-infected ones at four microsatellite loci are reported suggesting that resistance to the disease could have a genetic basis. Moreover, a positive or negative relationship between the frequency of certain alleles and the parasite infection was inferred. Further studies should confirm the potential use of those alleles as genetic markers forP. olseniinfection. Integrating results of genetic diversity within and between populations andPerkinsusinfection levels, a founder population for aR. decussatusbreeding program is proposed, composed by individuals from Barallobre (Rías Altas), Pontevedra or Cangas (Rías Baixas), Óbidos (North/Central Coast of Portugal), Algarve (Gulf of Cadiz) and Venice (Adriatic Sea).