Objectives <p>This study compares the proportional presence and the differences in means and medians of periodontal pathogens in cases of proliferative verrucous leukoplakia (PVL) versus patients diagnosed with oral lichen planus (OLP) with desquamative gingivitis (DG) and those with chronic periodontitis (CP).</p> Materials and methods <p>The study evaluated the presence of periodontal pathogens in 38 PVL cases verified by clinicopathological criteria, an equal number of histologically verified DG cases, and another 38 cases of CP. All patients were treated at the Oral Medicine Department of the Dentistry Clinic, Pilsen Faculty Hospital, between 2012 and 2024. All cohorts experienced CP with a similar level of progression (moderate, with approximately 6-millimeter-deep pockets). Twelve different periodontal pathogens were identified using DNA tests (VariOr-Dento). The study focused primarily on the aggressive pathogens classified within the red and orange complexes. The status of periodontal resorption was diagnosed through orthopantomograms and clinical examinations of periodontal pockets.</p> Results <p>The proportional dominance of red and orange complex periodontal pathogens in PVL was evident compared to gingival OLP and CP cases. PVL had the highest calculated risk for periodontal resorption and a greater mean number of aggressive bacteria per microliter.</p> Conclusion <p>Our research underscores the significant association between aggressive red and orange complex periodontal pathogens and PVL. In our study, PVL exhibited a threefold higher number of these bacteria than controls with CP. These findings may highlight an important cofactor in the pathogenesis of PVL.</p>