Systemic sclerosis (SS) is a rare severe autoimmune disease involving the connective tissue. The pathophysiology is not clearly understood. It is characterized by a remarkable clinical heterogeneity, and virtually all organs can be affected. Concerning diagnosis, the presence of antinuclear antibodies (ANA) can be found in more than 90% of patients, but the diagnosis is made gathering clinical manifestations, autoimmune panel, nailfold capillaroscopy and in some cases biopsy of the organ involved. The disease course is also weakly understood, although some serological patterns can be distinguished. Current therapeutic options target few aspects of pathologic mechanism and clinical management remains a challenge.The authors presented a rare case of a SS ANA negative, which demonstrates the diagnostic challenge of this disease.