The study aimed to validate the accuracy of Ki-67 (ICC marker) in identifying proliferative and malignant changes occurring in exfoliated buccal cells and compare it with the standard AgNOR staining technique. The study group comprised normal, smokers, and tobacco chewers, with a total of 30 subjects. The solutions for AgNOR staining were prepared as prescribed by Bukhari et al. (2007), and Ki-67 was used for ICC procedures. The AgNOR count was higher in smokers than in chewers. The AgNOR counts in chewers were also comparatively higher when compared to normal and close to smokers. The Immunocytochemistry (ICC) study showed positive expression of Ki-67 in the nucleus of exfoliated cells, which was significantly higher in chewers than in smokers and normal individuals. We conclude that ICC (Ki-67) is even more sensitive than AgNOR and can be used as an adjunct to histopathological investigations. As literature states that proliferation is observable with AgNOR, this holds true for the ICC technique with Ki-67 as well.