Introduction: Mixed Connective Tissue Disease (MCTD) has originally been described as a syndrome that consisted of a combination of features typically found in patients with Systemic lupus erythematosus (SLE), Systemic Sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), or rheumatoid arthritis (RA). Objective: The diagnosis of MCTD still remains controversial and it is critically dependent on the demonstration of high-titer anti-U1-RNP antibodies. When first described, MCTD, was believed to have a good prognosis. After longer follow-up studies this opinion has now been revisited: the prognosis in MCTD is in fact worse than that in LES, most of the deaths being due to pulmonary hypertension. The main question is whether or not MCTD patients have a distinctive clinical course, prognosis and treatment requirements. Conclusion: The importance of MCTD is not much in terms of diagnosis, but rather what antibody tells us about patients. The clinician must anticipate by treating the potential lethal complication of pulmonary hypertension, myositis and fibrosing alveolitis, and the tendency of the disease to evolve into one of its sister disease.