Proliferative leukoplakia (PL) is an uncommon yet aggressive variant of oral leukoplakia characterized by its high rates of malignant transformation and recurrence. Primarily affecting older, non-smoking females, PL can present as homogenous, verrucous, or erythroleukoplakia lesions. PL is associated with high DNA aneuploidy, alterations in tumor suppressor genes (TP53, CDKN2A), and exhibits immune evasion markers, such as PD-L1. Histopathologically, lesions may demonstrate architectural or cytologic dysplasia. Treatment of PL remains challenging with limited options. Recent findings support further research into molecular and immune-based therapies. There are current inconsistencies in terminology and diagnostic criteria for PL which emphasize the need for an international consensus to support standardized reporting, timely management, and conduct of clinical trials.