Given the essential role of prolactin (PRL) and its receptor (PRLR) in breast tumorigenesis, we investigated whether single nucleotide polymorphisms (SNPs) in the PRL and PRLR genes were associated with breast cancer in Taiwanese women. A total of 160 breast cancer patients and 336 unrelated control Taiwanese women were enrolled in this study. Three SNPs (rs1341238, rs2244502 and rs3756824) in the PRL gene and one SNP (rs10941235) in the PRLR gene were genotyped using allele-specific polymerase chain reaction and DNA sequencing. We showed that the PRLR SNP rs10941235 was associated with breast cancer (P\0.05) and its genotype frequencies in the breast cancer group were significantly associated (P\0.05) with the levels of cancer antigen 15-3, a serum biomarker of breast cancer. The PRL SNP rs3756824 was significantly associated with breast cancer metastasis (P\0.05). These findings suggest that the polymorphism rs10941235 in the PRLR gene is associated with breast cancer and cancer antigen 15-3 levels in Taiwanese women.