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Summary: The oral cavity is a highly regenerative epithelial tissue that results in minimal scarring after injury. This protocol describes the preparation of a mouse palate wound model. The protocol includes steps to place an excisional wound on the mouse palate, followed by harvesting of wound tissue and bone decalcification. We detail how to overcome the technical challenge of limited anatomical space, avoid damaging the nasal cavity, manage bleeding, and collect tissue for downstream genomic or immunohistochemical analysis. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.