The introduction of tests recognizing 'anti-citrullinated protein antibodies' (ACPA) has caused a revolution in rheumatology. Immunization against citrullinated proteins is a feature almost unique for rheumatoid arthritis, although ACPA may occur long before the onset of symptoms. Even if the presence of ACPA does not seem to reveal a distinct arthritis phenotype at symptom onset, it predicts an aggressive disease course with unfavourable outcome. Despite the very high diagnostic specificity for rheumatoid arthritis, ACPA-positivity does not always accord with a traditional diagnosis of rheumatoid arthritis at clinical presentation. However, even when these patients are judged to suffer from mild undifferentiated arthritis, they call for follow-up and special attention by rheumatologists.