There is growing evidence that personality traits are affected by many genes, all of which have very small effects. As an alternative to the largely unsuccessful search for individual polymorphisms associated with personality traits, the authors identified large sets of potentially related single nucleotide polymorphisms (SNPs) and summed them to form molecular personality scales (MPSs) with from 4 to 2,497 SNPs. Scales were derived from two thirds of a large (N = 3,972) sample of individuals from Sardinia who completed the Revised NEO Personality Inventory (P. T. Costa, Jr., & R. R. McCrae, 1992) and were assessed in a genomewide association scan. When MPSs were correlated with the phenotype in the remaining one third of the sample, very small but significant associations were found for 4 of the 5e personality factors when the longest scales were examined. These data suggest that MPSs for Neuroticism, Openness to Experience, Agreeableness, and Conscientiousness (but not Extraversion) contain genetic information that can be refined in future studies, and the procedures described here should be applicable to other quantitative traits.