Objectives: to determine the immunohistochemical expression of Podoplanin (PDPN) and p16- INK in oral cavity- and oropharyngeal squamous cell carcinoma (OSCC). Furthermore, we wanted to investigate the correlation between the expression of the two immunohistochemical factors and the histological characteristics of the tumor. Additional parameters analysed were the pathological stage, histological grade, age, gender, involvement of lymph node and lymphovascular- and perineural tissue. Materials and methods: retrospective study conducted at University Hospital of Split, Clinical Institute for Pathology, Forensic Medicine and Cytology, including 20 patients with OSCC in the period from January 1st 2015 until December 31st 2017. From the pathohistological findings, the following data were recorded: age and sex of the patient, localization of the tumor, histological grade of the tumor, the presence of lymphovascular and perineural invasion, the presence of grafts in the regional lymph nodes and the pathological stage of the disease (pT). Immunohistochemical analysis was performed using the method of double staining for PDPN and p16-INK. Results: A total of 70% of the patients were male and the mean age at the time of diagnosis was 66±12 years. There was no statistically significant difference in PDPN tumor expression in relation to patient gender (P=0.497), tumor size (P=0.597), tumor histological grade (P=0.217), presence of perineural (P=0.603) and lymphovascular invasion (P=0.603) as well as tumor involvement of lymph nodes (P=0.767). Stratified squamous epithelium (SSE) surrounding the tumor was PDPN negative (score 0) in 45% of cases, which was statistically significant (P=0.047). Majority of the tumors were p16-INK negative (P=0.004), as well as majority of SSE around the tumor (P=0.502). Majority of the tumors (65%) were moderately differentiated, 30% were well differentiated, and only 5% were poorly differentiated (P=0.004). Lymphovascular invasion was recorded in 35% of cases, and perineural in 40% of cases. The most common pathological stage of the disease was pT3. Conclusion: There were no statistically significant findings of PDNP in regard to histological characteristics of the tumor, local invasiveness or pathology stage of the disease. Only three tumors were p16-INK positive. Further studies are necessary in order to illuminate the role of PDPN and p16-INK in regards to OSCC characteristics.