OBJECTIVE Alpha B-Crystallin (CRYAB) is purported to be a metastasis suppressor protein, and lack or lower CRYAB expression is a prognostic biomarker for several types of cancer, such as that of the prostate and head and neck. However, the association of genomic variation of CRYAB and breast cancer is not well studied. The aim of this study was to evaluate the association of polymorphic genotypes of CRYAB with breast cancer within a Taiwanese population. METHODS In this hospital-based study, 1232 patients with breast cancer and an equal number of healthy controls in central Taiwan were genotyped via polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and the association of CRYAB A-1215G (rs2228387), C-802G (rs14133) and intron 2 (rs2070894) polymorphisms with breast cancer risk in a central Taiwanese population was investigated. RESULTS Those individuals with CRYAB C-802G CG and GG genotypes had 1.50- and 2.22-fold risk for breast cancer than those with the CC genotype. As for the A-1215G and intron 2 polymorphisms, there was no significant association of the genotype with breast cancer risk. In allelic frequency analysis, the G allele CRYAB C-802G conferred a significantly (p=5.63×10(-10)) increased risk of breast cancer. Our results provide evidence that the G allele of CRYAB C-802G is correlated with breast cancer risk and this polymorphism may be a useful marker for early detection of breast cancer in clinical practice.