Systemic sclerosis is characterized by a fibrosis and a microvascular injury. These vascular lesions can affect internal organs causing severe visceral damages. The pathogenesis of this disease is complex but some immunological disorders with a production of antinuclear auto-antibodies can be useful to the clinicians, especially for an early diagnosis and to distinguish the scleroderma/myositis overlap syndromes. This review presents the target antigens and the methods of detection of the different antinuclear auto-antibodies. Sensitivity, specificity and clinical association between the antinuclear auto-antibodies and the different subclasses of scleroderma are also presented in detail.