BACKGROUND: Numeric chromosomal imbalance, known as aneuploidy, is linked to both malignant and potentially malignant epithelial lesions. Aneuploidy has also been investigated in oral potentially malignant disorders (OPMDs) due to its high incidence in head and neck cancers, particularly in oral squamous cell carcinoma (OSCC). The study aimed to evaluate the potential of aneuploidy, a marker of chromosomal imbalance, as a prognostic tool for assessing malignant transformation risk in oral lichen planus (OLP) patients. METHODS: Fluorescent in situ hybridization (FISH) analysis targeting centromeric probes for chromosomes 2 and 8 was conducted on samples from 245 patients, with follow-up in 135 cases. RESULTS: Aneuploid cells (ACs) were detected in 73 patients (29.8%); 24 (32.9%) exhibited non-diploid cells in a normal looking mucosa. Only 2 (0.8%) patients developed OSCC during the follow-up. Among the 135 followed, 11 (8.1%) were positive for Acs in both samples, 15 (11.1%) were were negative initially but positive later. In contrast, 3 patients (2.2%) were initially positive but later negative. CONCLUSION: These results indicate a low malignant transformation rate (< 1%), despite a high rate of aneuploidy. These also demonstrate variability in aneuploidy results over time. The dynamic nature of aneuploidy observed suggests that it may not be a reliable predictive tool for malignant transformation in OLP.