Objectives: This multicentre case–control study aimed to investigate the potential association between oral lichen planus (OLP) and extraoral cancers. The secondary objective included the identification of risk factors for this association. Methods: The study was conducted between January 2023 and June 2024 and included 21 Italian Oral Medicine centres affiliated with the Italian Society of Oral Medicine (SIPMO). The study protocol was approved by the Ethics Committee of Università Cattolica del Sacro Cuore (Prot. ID 4073) and registered at clinicaltrials.gov (ID NCT06449248). Results: In total, 1650 participants were enrolled (550 OLP and 1100 non-OLP patients) matched for age and sex. OLP patients showed a significantly higher prevalence of extra-oral cancers (19.8%) compared to controls (12.4%) with a 1.79 OR (1.34–2.39, p < 0.05). Moreover, erosive OLP (n = 32/120, 26.7%, p < 0.01) and plaque-like variants (n = 27/114, 23.7%, p < 0.04) seem to have a slightly increased risk of extra-oral cancer. Conclusions: Patients with OLP had a higher risk of developing extraoral cancer; moreover, erosive and plaque-like forms could be considered at higher risk. Potential pathogenic mechanisms involve an interplay between chronic inflammation, immune dysregulation and carcinogenesis. Therefore, the directionality of such association remains unclear, underscoring the need for prospective studies to clarify causality and temporal dynamics.
