Chronic wounds were previously related to cancer. Chronic Traumatic Ulcers (CTU) are lesions caused by chronic mechanical irritation (CMI) frequently diagnosed in Oral Medicine. Although these conditions may reflect a benign nature, some authors have proposed its relationship with malignant transformation. Currently, there are scarce investigations that evaluate biomarkers within CTU. The aim of this study was to evaluate cell differentiation and proliferation biomarkers patterns of CTU and OSCC through recognized markers such as cytokeratin 19 and Ki67 and correlate it with clinical features of both groups of patients. A Cross-sectional study of adult patients (n=79), both sexes, attended at Oral Medicine Department, Facultad de Odontología, Universidad Nacional de Córdoba. The patients were classified into two groups: CTU (n=41), and OSCC (n=38). A subset of specimens were immunolabeled with Ki67 and Ck19. The population consisted of 51.9% male and 48.1% female, with an average of 57.0 ± 13.9. years (OSCC group) and 60.9 ± 14.9 years (CTU group). OSCC group presented higher scores for both biomarkers (Ki67 and Ck19), but only there were differences statistically significant for Ki67 (p=0.032). 25% of non-healing CTU were positive with medium scores of Ck19 and showed an immunohistochemical profile similar to OSCC. The lateral tongue was the most frequent site in both groups. The altered immunohistochemical pattern found in many specimens of CTU was also observed in OSCC. The tongue border presents physiological conditions that could offer a suitable environment for the development of neoplastic events associated with CMI. Further studies are needed to understand the underlying mechanisms that could link oral non-healing ulcers with early malignant changes.