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Background and Objectives: Oral squamous cell carcinoma (OSCC) is one of the most common tobacco-related cancers affecting the Indian population. Various malignancy-grading systems based on different histopathological features have been proposed for OSCC. Due to inherent subjectivity, interobserver variation and reproducibility of a grading system remains a problem. Grading systems based on nuclear morphometry have been proposed for laryngeal, renal and pharyngeal carcinomas. In this study, an attempt was made to grade oral OSCC based on computer-assisted microscopic evaluation of nuclear features. Our intention was also to evaluate the use of Feulgen stain for studying nuclear features. Materials and Methods: Sections made from buccal mucosa biopsies of normal mucosa as well as different grades OSCC were stained by Feulgen reaction. The nuclear features were evaluated by computer-assisted microscopic image analysis for nuclear area (NA), nuclear perimeter (NP) and nuclear form factor (NF) and correlated with histologic grading of OSCC. Nuclear shape, membrane outline, chromatin clumps, nucleoli, and abnormal mitoses were also evaluated. Results: NA and NP were observed to be significantly increased in OSCC (P < 0.001) when compared with the control group. These values increased in correlation with increasing grades of OSCC. However, NF was found to more in the control group (P < 0.001). Conclusion: It may be concluded from the results that computer-assisted nuclear morphometry is a reliable tool for grading OSCC. A new grading system based on nuclear features for OSCC has been proposed. [ABSTRACT FROM AUTHOR]