Background: Genomic instability is one of primary causes for malignant cell transformation. In this study induced genomic instability expressed as micronuclei in breast cancer (BC) patients with different stages of the disease compared with their unaffected first degree relatives (FDR) and normal unrelated controls was investigated. Materials and Methods: The background and net micronucleus frequency as well as other cellular damages induced after in vitro treatment with 25 µg/ml of bleomycin were evaluated using cytokinesis block micronucleus-cytome assay in peripheral blood lymphocytes of 120 Iranian individuals comprised of 40 BC patients, 40 FDRs and 40 normal control groups. Considering the protocol for each person total of 1,000 binucleated cells with well-preserved cytoplasm were blind scored on coded slides. Results: The net frequency of micronuclei was dramatically higher in breast cancer patients compared with controls. Also the net micronucleus (MN) frequency was significantly higher in FDRs compared with normal unrelated control. Considering cancer stages and clinical parameters, our results showed that the higher net frequency of MN was observed in higher stages and distant metastasis. Conclusion: This higher MN frequency both background and bleomycin induced in FDR compared with control group, clearly demonstrates that MN frequencies are determined by genetic factors to a major part and MN frequencies represent an intermediate phenotype between molecular DNA repair mechanisms and the cancer phenotype and affirms the approaches that are made to utilize them as predictors’ cancer risk . Also the association between MN frequency and metastasis proposes it as a possible prognostic marker.