Abstract: Objective: To screen serum biomarkers in patients with Paget's disease using surfaced enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) technique, and to find specific biomarkers which could be used for the early diagnosis of Paget's disease. Methods:The serum samples from 15 patients with Paget's disease, 10 patients with chronic eczema, and 10 healthy controls were detected with H50 proteinchip and SELDI-TOF-MS. The data were analyzed by Biomarker Patterns Software provided by Ciphergen Corp. A primary diagnosis model of Paget's disease was set up. Results: The structure of two proteins ( 3868Da and 8876Da) were significantly different in healthy people and Paget's disease patients ( P<0.01). Proteins of 2911Da, 3868Da, and 5097Da were significantly different between chronic eczema and Paget's disease (P<0.05). The M/Z values ranged from 2000Da to 30000 Da. The structure of the two proteins (3868Da and 8876Da) was significantly different among the three groups. A diagnostic pattern was established with a sensitivity of 73.3% and specificity of 100 % . Conclusion:SELDI-TOF-MS technique is a high-throughput proteomics approach with simple application, high sensitivity and remarkable specificity. SELDI-TOF-MS offers great promise in early diagnosis of Paget's disease and screening of tumor biomarkers.