A recent study identified a polymorphism (Pro86Leu) in the Calcium homeostasis modulator 1 (CALHM1) gene whose minor Leucine allele showed a higher frequency in Alzheimer's disease (AD) patients compared to controls (29% in AD and 22% in controls). Further studies provided conflicting results in different ethnic groups. In order to assess the involvement of the CALHM1 genetic variant on the risk of developing AD, we analyzed the genotype and allele distributions of the Pro86Leu polymorphism in 758 Italian subjects. Our results did not confirm an association between the CALHM1 variation and AD, thus suggesting a genetic heterogeneity among the various populations.