Most studies on the diagnostic utility of the anti-cyclic citrullinated peptide antibody (anti-CCP) test in rheumatoid arthritis (RA) have been performed in developed countries, with only a few done in the developing world. We undertook a cross-sectional study to determine the diagnostic utility of the rheumatoid factor (RF) and anti-CCP tests in urbanized Iranians with early RA. One hundred and ninety-three serum samples were obtained from consecutive patients who were diagnosed with RA. Serum samples of 254 ones without RA, consisting of other inflammatory polyarthritis disorders, were also collected as controls. RF was measured for IgM by latex agglutination test, and titers higher than 1/80 were considered positive. Anti-CCP was also assayed using an ELISA with 6.25 RU/ml as the threshold for a positive result. The anti-CCP had sensitivity, specificity, positive predictive value, and negative predictive value for a diagnosis of RA of 47.2, 92.9, 83.5, and 69.8 %, respectively. Those for RF were 57.0, 83.9, 72.8, and 72.0 %, respectively. For anti-CCP antibodies in combination with RF, they were 38.9, 96.5, 89.3, and 67.5 %, respectively. Anti-CCP has higher specificity and predictive values compared with the RF parameter in diagnosing RA in Iranian patients, but their discriminative values were similar. Anti-CCP and RF in combination further increases the diagnostic value for RA.