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Background/Purpose: Several previous studies have reported higher serum tumor marker levels in patients with oral or head and neck squamous cell carcinomas. This study evaluated whether 232 patients with oral precancerous lesions (oral precancer patients) had significantly higher serum carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and ferritin levels than healthy control subjects. Methods: The serum CEA, SCC-Ag, and ferritin levels in 232 oral precancer patients and 187 healthy control subjects were measured and compared. Patients with serum CEA level ≥3 ng/mL, SCC-Ag level ≥2 ng/mL, and ferritin level ≥250 ng/mL were scored as serum positive for CEA, SCC-Ag, and ferritin, respectively. Results: We found significantly higher mean serum CEA, SCC-Ag, and ferritin levels in 232 oral precancer patients than in 187 healthy control subjects (all P-values < 0.05). Moreover, 232 oral precancer patients had significantly higher serum positive rates of CEA (47.4%), SCC-Ag (13.8%), and ferritin (52.2%) than 187 healthy control subjects (all P-values < 0.05). Of the 232 oral precancer patients, 121 (52.1%), 56 (24.1%), and 10 (4.3%) had serum positivities of one, two, or three tumor markers including CEA, SCC-Ag, and ferritin, respectively. Conclusion: There are significantly higher mean serum CEA, SCC-Ag, and ferritin levels and significantly higher serum positive rates of CEA, SCC-Ag, and ferritin in oral precancer patients than in healthy control subjects. The serum CEA, SCC-Ag, and ferritin levels are of diagnostic value and may be potential tumor markers for the screening of oral precancer patients.