Numerous expert panels have concluded that there is sufficient evidence to classify involuntary smoking (or passive smoking) as carcinogenic to humans. The aim of this study is to establish whether passive smoking increases the frequency of chromosomal aberrations (CA) in peripheral blood lymphocytes compared to controls in Tamil Nadu, India. In the present study, CA increased with an increase in environmental tobacco smoke (ETS) and active smoke exposure period in passive smokers quantified on the basis of serum cotinine levels. The passive subjects were compared with healthy normal controls to validate the results. In conclusion, these data are compatible with the current knowledge on the mechanisms of carcinogenesis of tobacco-related cancers, occurring not only in active smokers but with a high biological plausibility also in passive smokers.