Background: Cancer burden can be reduced by early detection of early neoplastic changes applying suitable screening methods. This study aimed to assess the utility of nucleolar organizer regions (NORs) quantitation in early prediction of lung neoplastic transformation. Methodology: This study investigated 200 apparently healthy individuals categorized into two groups; smoking exposed individuals (N=100), and were categorized as cases, and smoking nonexposed (N=100), and were ascertained as controls. Sputum specimen was attained from each participant (paying all indispensable safety precautions and sample adequacy processes). Results: Out of the 200 volunteers assessed in the present study, mean NORs counts of >2.00 were identified in 16/200(8%) of the study subjects. All 16/16(100%) cases were found with lung epithelial metaplasia (squamous metaplasia). Out of the 100 cases, mean NORs counts of >2.00 were identified in 16/100(16%), hence, all the controls were identified with mean NORs counts of <2.00. The risk of lung cellular proliferative changes associated with smoking exposure are odds ratio (OR) (95% confidence interval, CI) = 39.2485 (2.3199-664.0052), p = 0.0110, z statistic = 2.543. Conclusion: NORs count is a simple, specific, cost-effective, and reliable method that can give a quantitative measurement for the risk of lung neoplastic transformation. For at risk-population (tobacco users), it is recommended to perform the argyrophilic NORs (AgNORs) method beside sputum cytology.