Background: Modified Cajal's trichrome stain (MCTS) is a good differential stain that allows one to visibly distinguish between connective tissue and epithelial elements with different tonalities of colour. Aim: Our study aims to evaluate and analyse the effectiveness of oral squamous cell carcinoma (OSCC) using MCTS. Materials and Methods: A study was conducted retrospectively with 30 tissue blocks embedded in paraffin from cases of OSCC that have been confirmed by histopathology. Both standard haematoxylin and eosin (H&E) and MCTS were applied to each section. Then all the sections were analysed by two observers for nucleus cytoplasmic intensity, break in the basement membrane, and advancing front of the tumour, muscle, and surrounding stroma. The efficacy of the stain was assessed and was graded as 1, poor; 2, fair; and 3, good based on the staining intensity. Statistical Analysis: The parameters were graded for H&E and modified Cajal's stain. The results were subjected to the Chi-square test. Result: The above-mentioned parameters analysed showed a uniformly significant P value of 0.001 for comparing modified Cajal's trichrome stain to H&E stain. Measurement of the agreement was done based on Kappa statistics between two observers, and the values for each expression show that there was good agreement between the two for all the parameters. Conclusion: MCTS can also be used as a diagnostic aid to pathologists for better distinction of cellular components and easier identification, thereby solving difficulties in diagnosis at earlier stages. © 2024 Elsevier B.V., All rights reserved.