ObjectiveTo evaluate the cytological changes of the oral mucosa among smokers using Argyrophilic nucleolar organizer region (AgNOR) counts and Papanicolaou (Pap) staining.MethodologyThe oral mucosal exfoliate smears of 500 individuals (200 nonsmokers and 300 smokers) aged between 18 and 80 years were prepared in Al Madinah. The AgNOR count and Pap stain were used to generate a cytogenic smear to assess the presence of cytological changes suggestive of atypia, inflammation, dysplasia, keratinization, and proliferative activity of epithelial cells.ResultsSmokers have a considerably higher number of AgNORs per nucleus than nonsmokers (1.99 3.53 vs. 0.42 1.22). There were inflammatory changes in 127 (42.3%) of the cases and 40 (20%) of the controls. Multinucleated cells and atypia were found in 33 (11%) and 14 (4.5%) of the cases but not in the controls. The results indicate higher proliferative activity in smoking patients compared to nonsmoking patients, even in the absence of clinical lesions.ConclusionTo detect the effects of smoking on the oral mucosa, Pap staining alone is insufficient. Combining Pap staining with the AgNOR technique produces the desired results.