Background: Biopsy is a critical procedure in the diagnosis and treatment plan of surgical cases and is also highly technique-sensitive. Various biopsy techniques are conventionally used with each technique having its own pros and cons. A study was carried out to compare scalpel versus Punch for biopsy of oral lesions under various parameters vital to histopathological diagnosis. Materials and Methods: A total of 16 patients (08 in each group) satisfying the inclusion criteria were randomly allocated using odd-even scheme into scalpel and Punch groups by a operator. The patients were evaluated intraoperatively for patient comfort, bleeding, time taken for excision, and postoperatively for pain and healing. The excised samples were sent for histopathological analysis as follows: Loss of architecture in epithelium, loss of architecture in connective tissue and artifacts. Results: The mean time taken for excision was statistically similar in both the groups. Distribution of patient comfort and pain was statistically not significant. Healing was uneventful in both the groups. In the histological parameters, there was loss of architecture in epithelium in many cases in the punch group. In the same group, there was loss of architecture in the samples. Conclusion: Both techniques seem to be equally effective in performing incisional biopsies of oral lesions. Punch biopsy has the advantage of fast and avoidance of suturing as well. However, due to the Size of tissue caused, there may be minor loss of histological architecture.