SummaryStudies on the extent of DNA damage are undertaken to elucidate the nature and causes of genomic instability in any syndrome or disease progression in human. In this study, cytokinesis-block micronucleus cytome (CBMN Cyt) assay was employed to evaluate the extent of chromosomal instability or DNA damage in lymphocytes of patients suffering from dilated cardiomyopathy (DCM), a serious cardiac muscle disorder. Effect of DNA damage on the disease was also assessed by analysis of mutations in cardiac Troponin C type I (TNNC1) gene. Blood samples were collected from 48 DCM patients and 48 age- and sex-matched controls from Vellore region of South India. Significantly high frequencies of micronuclei (MNi) and genomic damage such as nuclear buds (NBUDs) and nucleoplasmic bridges (NPBs) were observed in the patient group as compared with the control group (P< 0·001). Molecular analysis revealed that no mutations were found in the TNNC1 gene. It was observed that although there was a high frequency of DNA damage in the lymphocytes of the patients, no correlation between severity of the phenotype and the frequencies of MNi, NPBs and NBUDS could be established. Our study appears to be the first one in which chromosomal instability was estimated using CBMN Cyt assay for DCM patients. Studies with a larger population size may help in validating the use of genetic markers for establishing frequencies and type of DNA damage in DCM. It will also help in understanding the effect of DNA damage on this disease.