Associations of antinuclear (ANA) and anticardiolipin (aCL) antibodies with clinical manifestations were analyzed in patients with systemic sclerosis (SSc). We studied 105 SSc patients: 28 had limited cutaneous SSc (lcSSc) involving fingers; 36 had intermediate cutaneous SSc involving limbs and face; 33 had diffuse cutaneous SSc (dcSSc) involving the trunk; 8 had a sclerosis sine scleroderma. Clinical manifestations and instrumental and laboratory findings were considered to calculate a disease score. Serum anticentromere (ACA), anti-topoisomerase I (anti-topo I) antibodies, and aCL (of IgG/IgA/IgM classes) were investigated by conventional methods. ACA positive patients (n=18), compared to ACA negative, showed higher prevalence of IcSSc (p < 0.001), lower prevalence of restrictive ventilatory defect (p=0.006), and lower disease score (p=0.008). Anti-topo I positive patients (n= 70) showed lower prevalence of lcSSc (p =0.001) compared to anti-topo I negative. In aCL positive patients (n=27) widespread skin and visceral involvement occurred more frequently than in aCL negative. The association with myocardial ischemia or necrosis (p=0.010) was significant. Occurrence of ACA excluded the coexistence of anti-topo I (p < 0.001), and aCL (p=0.037). aCL positive patients showed higher disease score in comparison with ACA positive patients (p=0.003). In conclusion ACA recognize patients with a mild disease. aCL in contrast to ACA are better than anti-topo I in recognizing the most severe pictures of SSc.