Aims: This retrospective cohort study aims to address gaps and inconsistency in evidence regarding the prevalence and prognostic significance of OSCC arising from documented known mucosal changes (OSCC-KMC), and to determine whether prior identification of precursor lesions translates into a measurable survival benefits. Methods: We performed a retrospective cohort study of 285 patients diagnosed with OSCC (2007–2013), comparing tumours arising from known mucosal changes (OSCC-KMC; n=92) with de novo OSCC (OSCC-dn; n=193). Demographics, risk factors, referral and biopsy pathways, clinicopathological characteristics, and survival outcomes were analysed. Results: OSCC-KMC accounted for 32.3% of cases. Compared with OSCC-dn, OSCC-KMC patients were more often female (60.9% vs 33.7%, p<0.001) and more frequently reported no smoking or alcohol history (59.8% vs 12.4%, p<0.001). Before malignant transformation, 59% of mucosal lesions had histopathological assessment, with specialists having higher biopsy rate than generalists (p<0.001). At presentation, OSCC-KMC more commonly lacked nodal disease (p=0.002) and had lower clinical stage (p=0.043). Despite these favourable baseline features, OSCC-KMC showed higher overall recurrence (27.2% vs 13.0%, p=0.005) and more late recurrences beyond five years (10.9% vs 4.1%, p=0.038). On multivariable analysis, a history of known mucosal change independently predicted disease-specific mortality (HR 2.00, p=0.013). Conclusion: OSCC-KMC appears to represent a distinct clinical phenotype with paradoxical outcomes. Despite earlier-stage presentation in lower-risk demographics, OSCC-KMC tend to present with including increased recurrence rate and higher disease-specific mortality. These findings support prolonged, potentially lifelong, postoperative surveillance beyond the conventional five-year period for patients with OSCC-KMC.