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Objective: The aim of this study was to evaluate the postoperative course in patients undergoing oral mucosal biopsies, considering clinical and patient’s perception variables potentially correlated to poor healing. Subjects and methods: Eighty patients underwent oral biopsies. All the variables connected with the surgery were recorded, and the harvested volume was calculated through image software (ImageJ, NIH, Betesda, USA). To evaluate the postoperative discomfort, the OHIP-14 and the numeric rating scale of pain (NRS) were administered at 6 h, 7 days and 21 days after biopsy. Results: Six hours after the biopsy, 22 (OHIP-14 ≥ 20) and 24 (NRS ≥ 4) patients experienced a troublesome or painful healing, respectively. A significant statistical correlation between poor healing and high scores of NRS and OHIP was detected (Pearson’s correlation test p < 0.05). Higher values of OHIP-14 were correlated to the type of lesion (OR = 1.165; p < 0.05), whereas high values of NRS were correlated to the use of systemic drugs (p < 0.05). No surgical variable had a significant statistical correlation with any of the outcomes. Conclusions: The clinical evaluation was correlated with the patient’s perception of pain and discomfort. This finding could be suggestive of the fact that wound healing can be reliably monitored with the help of these tools. Clinical relevance: Patient perception can be a predictor of the healing of biopsied tissues.