Collectively, this study reveals molecular processes associated with PML progression that may help early diagnosis and disease interception at an early stage.<h4>Author summary</h4>Patients harboring oral premalignant lesions (PMLs) have an increased risk of developing oral squamous cell carcinoma (OSCC), but the underlying mechanisms driving transformation of PMLs to OSCC remain poorly understood. The gene discussed is PML; the disease is oral cavity squamous cell carcinoma.