Background: Diagnostic imaging plays a relevant role in the care of patients with breast cancer (BC). PositronEmission Tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG) has been widely proven to be a clinical toolsuitable for BC detection and staging in which the glucose analog supplies metabolic information about the tumor.A limited number of studies, sometimes controversial, describe possible associations between FDG uptake andsingle nucleotide polymorphisms (SNPs). For this reason this field has to be explored and clarified. We investigatedthe association of SNPs in GLUT1, HIF-1a, EPAS1, APEX1, VEGFA and MTHFR genes with the FDG uptake in BC.Methods: In 26 caucasian individuals with primary BC, whole-body PET-CT scans were obtained and quantitativeanalysis was performed by calculating the maximum Standardized Uptake Value normalized to body-weight(SUVmax) and the mean SUV normalized to body-weight corrected for partial volume effect (SUVpvc). Human GeneMutation Database and dbSNP Short Genetic Variations database were used to analyze gene regions containing theselected SNPs. Patient genotypes were obtained using Sanger DNA sequencing analysis performed by CapillaryElectrophoresis.Results: BC patients were genotyped for the following nine SNPs: GLUT1: rs841853 and rs710218; HIF-1a:rs11549465 and rs11549467; EPAS1: rs137853037 and rs137853036; APEX1: rs1130409; VEGFA: rs3025039 and MTHFR:rs1801133. In this work correlations between the nine potentially useful polymorphisms selected and previouslysuggested with tracer uptake (using both SUVmax and SUVpvc) were not found.Conclusions: The possible functional influence of specific SNPs on FDG uptake needs further studies in humancancer. In summary, this is the first pilot study, to our knowledge, which investigates the association between alarge panel of SNPs and FDG uptake specifically in BC patients. This work represents a multidisciplinary andtranslational medicine approach to study BC where, the possible correlation between SNPs and tracer uptake, maybe considered to improve personalized cancer treatment and care.