Aim: Squamous cell carcinoma is the most common malignancy affecting the oral cavity. In spite of advanced therapeutic interventions, it is still a common cause of morbidity and mortality worldwide. The clinical presentation and prognosis of the carcinomas occurring at different sites in the oral cavity is varied and could be explained by the difference in the type of epithelia from which they originate. Therefore this study aimed to assess the patient and tumor characteristics, clinical presentation and behavior of a sample of oral squamous cell carcinomas (OSCC) to determine the parameters most likely to influence the prognosis based on the origin of the epithelium. Materials and methods: Eighty-nine cases of histologicallyproven oral squamous cell carcinoma with a minimum followup of three years were categorized based on their epithelia of origin. The clinical follow-up data and survival were collected from the patient's records. New malignancy grading by Anneroth et al. was utilized for histopathological grading following which the lymph nodes (in cases of neck dissection) were assessed for evidence of nodal metastasis. Results: Most of the carcinomas originated from the nonkeratinized epithelium (42.7% n = 38) followed by the keratinized epithelium. Carcinomas arising from the non-keratinized epithelium had the poorest outcome with a mortality of 27.7% (n = 10) and disease-free survival of 38.8% (n = 14) at the end of 36 months. Conclusion: The present study though limited in its sample size and follow-up concluded that the nature of epithelium of origin has a bearing on the prognosis of oral squamous cell carcinoma. Clinical significance: Knowledge of the prognostic significance of the oral squamous cell carcinomas based on the type of epithelia of origin will help the clinicians to plan a more aggressive treatment plan for patients with carcinomas originating from the non-keratinized epithelium.