Epidermal cysts are intradermal or subcutaneous cystic tumors that frequently occur in the face, scalp, neck, and body trunk. Acquired cases of epidermal cyst commonly occur as a result of various surgical operations, chronic irritation, or trauma, all of which may trigger the occurrence of the invagination of squamous epithelium. A 57-year-old man presented with a palpable mass 7 cm×2 cm in size in the upper lip. The patient had a 3-year history of wearing a denture to restore missing bilateral maxillary central and lateral incisors, accompanied by inflammatory findings on the buccal mucosa due to chronic lip irritation. The resected oval-shaped cyst had a size of 5.5 cm×3.0 cm×2.5 cm, and it was an encapsulated mass with a well-defined margin. The histopathology was typical of epidermal cyst. This case of a rare giant upper lip epidermal cyst in a patient wearing a denture may be of interest to clinicians.