Background: Breast cancer is the most commonly occurring and leading among cancer death in women worldwide. Though an integral part of cancer therapeutics, chemotherapy can cause adverse side effects in normal tissues of the patients. Genotoxic side effects caused by chemotherapy are highly variable among patients. In this study, we assessed the genomic instability in female breast cancer patients using the Cytokinesis Block Micronuclear Cytome Assay in peripheral blood lymphocytes from female breast cancer patients (n=50) before and after chemotherapy. Materials &Method: Samples from fifty female breast cancer patients (stage IB to IIIB) before and after chemotherapy were collected for this comparative observational study from Department of Radiotherapy, Government Medical College, Alappuzha. Frequency of DNA damage endpoints such as Micronuclei (MNi), Nucleoplasmic Bridges (NPB) and Nuclear Buds (NBUDs) are scored after performing cytokinesis block micronuclei cytome assay (CBMN Cyt Assay). Result: In Breast cancer patients, comparison of CBMN Cyt assay parameters before and after chemotherapy showed that the frequency of Micronuclei (MNi) (before- 13.32±4.64; after- 21.38±4.72), Nucleoplasmic bridges (NPB) (before -2.3±1.65; after-10.5±1.75) and Nuclearbuds(NBUD) (before-3.32±1.63; after-11.58±1.57) were significantly higher after chemotherapy (p<0.0001). Cytokinesis-block proliferation index (CBPI) was also statistically significant when compared, before (1.69±.054) and after (1.66±.02) chemotherapy in breast cancer patients with a p value of 0.003 Conclusion: There was a significant increase in the frequency of genomic instability markers (MNi, NPB and NBUD) in female breast cancer patients after chemotherapy compared to the baseline data. We can conclude that the increase in the genomic instability markers were due to the damage in genetic contents as a result of neoplasm and it increased after chemotherapy. Genotoxicity caused by antineoplastic drugs can cause cell destruction and cell death in the peripheral lymphocytes. The decrease in CBPI also indicates the cytotoxicity of the drugs, which resulted in the low proliferation rate due to the genotoxicity induced cell death. Our results con firm the genotoxic and the cytotoxic effects of antineoplastic drugs in blood lymphocytes circulation.