BACKGROUND: Despite its unsatisfactory specificity, rheumatoid factor (RF) is the only serologic marker included in the diagnostic criteria of the American College of Rheumatology (ACR) for rheumatoid arthritis. Recently, the diagnostic value of anti-cyclic citrullinated peptide (CCP) antibodies has been emphasized in rheumatoid arthritis (RA) due to its high specificity. To evaluate the second generation of anti-CCP antibodies as a diagnostic marker, we evaluated anti-CCP test in 163 individuals. METHODS: The study population was divided into the following four groups: RA group (n=18), other disease group with arthritic symptoms (n=44), other disease group without arthritic symptoms (n=45), and healthy group (n=56). Anti-CCP was measured by an ELISA analyzer (Coda, Bio-Rad, USA) with Immunoscan RA (Euro-Diagnostica, Malmo, Sweden) and RF was measured by an automated chemistry analyzer (Toshiba, Japan) with RF-LATEX X1 (Denka Seiken, Japan). RESULTS: The sensitivity of anti-CCP and RF was 72.2% and 100%, respectively, and the respective figures for the specificity were 96.6% and 73%. On each ROC curve, the area under the curve was 0.867 for anti-CCP and 0.959 for RF. In other disease groups, most of the false positive cases of RF were found in the patients with hyperlipidemia or HBV carriage. However, anti-CCP was not detected in any of the patients with these two conditions. False positive rates of RF in the three control groups were 34.1% in other disease group with arthritic symptoms, 48.9% in the other disease group without arthritic symptoms, and 3.6% in healthy group. The respective figures for anti-CCP were 6.8%, 2.2%, and 1.8%. CONCLUSIONS: The specificity of anti-CCP antibodies was higher than that of RF for discriminating RA from other diseases, especially in the patients with hyperlipidemia or HBV carriage. With its high specificity, anti-CCP antibodies can play an additive role in establishing the diagnosis of RA in patients with RF positivity.