Genome-wide association studies have identified novel breast cancer susceptibility loci at 12q24 (rs1292011), 12p11 (rs10771399) and 21q21 (rs2823093). The aim of our study was to investigate the prevalence of variants at these three loci in an Irish sample, and to examine the association between these variants and breast cancer in this cohort. DNA was extracted from the blood or buccal swabs of Irish patients with breast cancer (cases), as well as from healthy Irish female controls. Genotyping was performed for each target using a Taqman-based platform. Data were analysed using IBM Statistical Package for the Social Sciences version 22. Genotyping was performed on samples from 1,267 patients with breast cancer and 841 cancer-free controls. The per-allele odds ratio associated with the minor allele at 12p11 was found to be 0.67 (0.54-0.81, p < 0.001). Genotype-specific odds ratios showed an allele dosage effect with odds ratio of 0.76 (0.6-0.95) for heterozygotes, and 0.23 (0.1-0.51) for rare homozygotes. Minor allele frequencies of the variants at 12q24 and 21q21 did not differ significantly between cases or controls. All three investigated variants were identified in the Irish population. The polymorphism rs10771399 was strongly associated with breast cancer risk in this cohort, and was shown to be associated with reduced odds ratio for all molecular subtypes.