Antiphospholipid syndrome (APS) can be either primary or secondary to autoimmune diseases, malignancies, infectious diseases, or drug-induced conditions. The aim of this study was to describe a novel overlap syndrome of APS and systemic sclerosis (SSc) in a case series. A retrospective review of medical files of hospitalized patients who were followed in two rheumatology clinics in Israel for the diagnosis of SSc and APS was sought. A MEDLINE search was performed for reports of APS/SSc overlap syndrome. Five patients with the overlap syndrome of APS and SSc were retrieved. The diagnosis of both diseases was confirmed by the American College of Rheumatology classification criteria. Four patients were women and of an older age group (42-68 years old). Three patients had primary APS, and in two patients APS was secondary to SSc. Two of the five patients died. The interval between APS and SSc was < 1-18 years. APS/SSc overlap syndrome is described for the first time as a case series. The patients may be older, with an interval of up to 18 years between diseases. The APS patients did not suffer from SLE. The overlap syndrome was characterized in certain instances with severe disease and two patients died. With relevant clinical manifestations, APS should be sought in SSc patients and treated appropriately.