The presence of IgM class rheumatoid factor (RF-M) in the serum is one of the ACR criteria for the classification of rheumatoid arthritis (RA). Objectives: To compare the sensitivity and specificity of two diagnostic markers for RA in Portuguese patients: the 2nd generation anti-cyclic citrullinated peptide antibodies (anti-CCP2) and the RF-M. Methods: Serum samples from 56 patients with established RA (44 women and 12 men, mean disease duration 9,5 +/- 8,5 years) were evaluated for the presence of anti-CCP2 and RF-M. Results were compared with 93 samples from a control group with identical demographic characteristics (43 from patients with spondylarthropaties and 50 from healthy blood donors). The determination of anti-CCP, antibodies was performed by enzymatic fluroimunoassay and RF-M was measured by microElisa. Results: Anti-CCP2 antibodies were positive in 40 patients with RA (71,4%) at a mean antibody concentration of 350,5 UA/ml (range: 11-1670 UA/ml) and negative in all controls. The RF-M was positive in 34 patients with RA (60,7%), in 4 patients with spondylarthropaties (9,3%) and in one blood donor (2%). The sensitivity, specificity, positive predictive value and negative predictive value for RF-M was 60,7%, 90,7%, 89,5% and 63,9% and for anti-CCP2 was 71,4%, 100%, 100% and 72,9% respectively. Conclusions: The anti-CCP, assay showed an excellent specificity and a global performance superior to that of the RF-M test in this population with established RA.