Introduction: Mast cells are important stromal elements, with different roles in tumorigenesis, including their effect on tumor growth, progression, differentiation and invasion. Histologic grading shows tumor differentiation and is used to predict the invasive behavior of various tumors, including oral squamous cell carcinoma (OSCC). The aim of the present study was to evaluate and mast cell density (MCD) and its relationship with different grades of OSCC based on three different valid grading systems.Materials and methods: In this experimental study, 42 histologic block samples of OSCC were retrieved from the archives of Cancer Institute, Tehran University of Medical Sciences, based on inclusion and exclusion criteria. After hematoxylin and eosin staining of the sections, they were graded according to the methods described by Broder, Anneroth and Bryne. All the samples were subjected to toluidine-blue staining and MCD was determined in 10 fields at ×40. The results were analyzed using one-way ANOVA (a=0.05).Results: Means ± standard deviations of MCD in low-, intermediate- and high-grade tumors were 42.07±23.45, 33±20.32 and 24.92±15.81 according to Broder; 36.08±27.88, 34.38±19.85 and 27±6.32 based on Bryne and 33.25±26.35, 33.50±18.99 and 34.46±21.92 using the Anneroth system, respectively. There were no significant differences in MCD between different OSCC grades in any of the three grading systems (p value=0.11, p value=0.68, p value=0.99).Conclusion: Based on the results of the present study, there is no relationship between MCD in OSCC and the tumor grade in the three grading systems evaluated in this study.