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Caliber persistent artery (CPA) is a vascular anomaly presenting as a bluish and pulsatile artery in the subepithelial tissue. Although the incidence of CPA was debated, many CPAs occurred in the perioral and facial tissues at which the embryonal strapedial artery networks were distributed. The present study demonstrated a case of CPA occurred in the retromolar buccal mucosa in a 37 years old male. The lesion showed many pinkish granular spots, but was asymptomatic except biting irritation during mastication. It had slowly increased in size up to 20 × 25 mm for 3 years, and recently became hemorrhagic due to the biting injury between left upper and lower second molars. With the fear of oral cancer an incisional biopsy was performed, and followed by histological and immunohistochemical study. Histologically the lesion showed many tortuous artery localized at the submucosa area, and the arterial wall was thick and its lumen was narrowed and shrunken. In the immunochemistry α-SMA was positive for thick smooth muscle layer of artery and arterioles, TGase 2 was weakly positive for the luminal surface of arterial intima, and bFGF was consistently positive for the perivascular fibrous tissue. But PCNA, VEGF, CD31, CMG2, TGF-β1, HSP-70, and 14-3-3 were almost negative for the vascular tissue. Therefore, it was presumed that the lesion was not actively proliferative nor degenerative but still retained its cellular stability and slow growing potential. It was finally diagnosed as CPA differentially from arterio-venous malformation, hemangioma, lymphangioma, and squamous cell carcinoma. The retromolar buccal mucosa CPA is first reported in this study and may present usual clinical findings depending on its size and location. This asymptomatic lesion could be severely hemorrhagic by minor biting injury, therefore, precise differential diagnosis should be made through biopsy, and careful therapy be followed.