This study was planned to investigate the feasibility of nucleus accumbens-associated protein 1（NAC1） for distinguishing oral malignancies from non-malignancies. Subjects comprised 165 patients including 32 with lichen planus, 19 with hyperkeratosis, 67 with epithelial dysplasia, 10 with carcinoma in situ, and 37 with oral squamous cell carcinoma （OSCC）. Normal oral mucosa （NOE） was taken from 15 healthy participants. NAC1 labeling indices （LIs） and NAC1 immunoreactivity intensity were examined. In OSCC, the correlation between clinical behavior and NAC1 expression was also examined. NAC1 expression was stronger in NOE and OSCC, but weaker in other lesions. NAC1 LIs correlated strongly with NAC1 immunoreactivity intensity. No correlation was observed between NAC1 LIs/NAC1 immunoreactivity intensity and tumor behavior such as lymph node involvement in OSCC. Though there were differences in NAC1 expression in various oral lesions, NAC1 is not a definitive marker for distinguishing oral malignancies from non-malignancies.