Aim and objective: To define the genotoxic potential of tobacco and alcohol in the oral mucosa through a micronuclei (MN) test. Materials and methods: Samples of exfoliative cells from oral mucosa were collected using superficial scraping of the right- and left-cheek mucosa of 83 patients divided into four groups, namely: (G1) 24 individuals abstaining from tobacco and alcoholic beverages; (G2) 23 individuals who smoke and abstain from alcoholic beverages; (G3) 24 smokers and alcoholics; and (G4) 12 individuals who consume alcohol and abstain from tobacco. The samples were stained with Giemsa-Wright, and the frequencies of MN, binucleated cells, and metanuclear changes were recorded in the samples of each group (1,000 cells per patient). Results: Analysis of variance (ANOVA) showed a difference between groups for changes concerning karyorrhexis (p = 0), pycnosis (p = 0.002), karyolysis (p = 0.003), and binucleated cells (p = 0.046). As for the total number of changes, G3, G2, and G4, respectively, were significantly higher than G1. Conclusion: It is suggested that the influence of smoking and drinking on exfoliating cells of oral mucosa may cause metanuclear changes due to genetic changes that these products cause, and the MN test is effective in detecting and monitoring such changes. Clinical significance: MN test may work for constantly monitoring the oral mucosa of smokers and/or alcoholic patients, so that early cell changes may be diagnosed, preventing the genesis of oral cancer.