Diabetes mellitus is one of the chronic systemic disorders with major influences of the oral cavity microenvironment. Oral manifestations of diabetes are diverse; they are represented by candidose, lichen plan, recurrent aphthous stomatitis, gingivitis, salivary disorders, oral mucosa atrophy and rarely hypertrophy; a possible link between oral cancer and diabetes is suspected, both in animal models and humans. We report a case of a young woman with type 1 diabetes with class I Kennedy edentation with mobile denture prosthesis; latter in the clinical follow-up, a hyperplasic lesion of the oral mucosa with p53 expression within the epithelial nuclei was identified, p53 being the more likely pathogenic pathway involved in diabetes-related oral cancer. The approach of this patient required multidisciplinary investigations and careful follow-up.