Background: In recent days, tissue eosinophils are considered to have more impetus role in the biological behavior of various tumors. Compared to routine hematoxylin and eosin stain, the special stains such as carbol chromotrope for eosinophils are considered to be more specific and definitive for its evaluation in routine histopathology. Aim: This study aims to evaluate and compare the infiltration of tissue eosinophils in different grades of oral squamous cell carcinoma (OSCC) using a special stain – carbol chromotrope and to investigate the prognostic role of tissue eosinophils in OSCC. Methodology: The study was carried out with the sample size of fifty histopathologically diagnosed cases of OSCC, of which twenty cases were well differentiated, twenty cases were moderately differentiated, and ten cases were poorly differentiated, and comparison of infiltration of tissue eosinophils in the different grades of OSCC was done using special stain. The tissue sections were stained with carbol chromotrope special stain. Results: In the present study, more number of tissue eosinophils were seen in well‑differentiated OSCC cases than the moderately and poorly differentiated OSCC cases, and the analysis of variance test showed P < 0.001. Tukey B’s post hoc range test showed that mean scores fell in three different subsets, and the least mean score was observed in the poorly differentiated group (2.20) and the highest mean score was observed in the well‑differentiated group (34.75). Conclusion: The results proved that the presence of more number of tissue eosinophils in well‑differentiated OSCC is associated with favorable prognosis and that quantitative assessment of tissue eosinophilia should become a part of the routine histopathological diagnosis for the different grades of OSCC. © 2024 Elsevier B.V., All rights reserved.