Breast cancer is considered a major malignancy among women worldwide. The contribution of genetic elements to the onset of familial breast cancer has already been established. The current study investigate the alfele frequency of HLA-DRB 1 in 36 primary operable female breast cancer patients from southern Iran by polymerase chain reaction using sequence specific primers (PCR-SSP). Results were compared with those of 36 female control subjects. Statistical analysis was performed and P values were determined for each character. Our results indicated that the frequency of HLA-DRB 1*12 allele is significantly higher in the patient group (p<0.03) compared to the control group. In addition, HLA-DRB1*11 appeared to be as the most frequent allele in the control group (29.2%) and had approximately the same distribution among the patient group (22.5%).