PVL (proliferative verrucous leukoplakia) has distinct clinical characteristics. They have a proclivity for multifocality, a high recurrence rate after treatment, and malignant transformation, and they can progress to verrucous or squamous cell carcinoma. AI can aid in the diagnosis and prognosis of cancers and other diseases. Computational algorithms can spot tissue changes that a pathologist might overlook. This method is only used in a few studies to diagnose LB and PVL. To see if their cellular nuclei differed and if this cellular compartment could classify them, researchers used a computational system and a polynomial classifier to compare OLs and PVLs. 161 OL and 3 PVL specimens in the lab were grown, photographed, and used for training and computation. Exam orders revealed patients’ sociodemographics and clinical pathologies. The nucleus was segmented using Mask R-CNN, and LB and PVL were classified using a polynomial classifier based on nucleus area, perimeter, eccentricity, orientation, solidity, entropies, and Moran Index (a measure of disorderliness). The majority of OL patients were male smokers; most PVL patients were female, with a third having malignant transformation. The neural network correctly identified cell nuclei 92.95% of the time. Except for solidity, 11 of the 13 nuclear characteristics compared between the PVL and the LB showed significant differences. The 97.6% under the curve of the polynomial classifier was used to classify the two lesions. These results demonstrate that computational methods can aid in diagnosing these two lesions.