Introduction: Cancer-associated fibroblasts (CAFs) from the tumor microenvironment (TME) play an important role in the progression, recurrence and poor prognosis of OSCC. The aim: To determine the density of CAFs in the tumorstroma (TS) of OSCC, and to determine the association of the density of CAFs with clinico-pathological parameters and disease relapse in patients with OSCC. Materials and methods: Immunohistochemical staining of tissue samples from primary OSCC was performed in 45 patients operated at the University Clinic for Maxillofacial Surgery, in Skopje, North Macedonia. A mouse primary monoclonal antibody: anti-a-SMA was used to visualize CAFs. The density of CAFs aSMA+ was grouped into 4 grades, and the obtained data were statistically analyzed. Results: The presence of CAFs was not determined in tissue samples from all patients with OSCC. There is a significant association of the density of CAFs in the primary tumor with T, N and TNM-status, respectively (p=0.0006, p=0.0255, p=0.0164). The Difference test determined that only in case of disease relapse in the form of local recurrence, the percentage representation of patients with CAFs present was significantly higher compared to patients who did not have CAFs (p=0.0001). Conclusions: These findings are suggestive of the role of CAFs in disease progression, but are insufficient to be included as a parameter in a standardized histopathological finding.