Antiphospholipid antibody (APLA) is a family of antibody that exhibits a broad range of target specificities and affinities all recognizing various combination of phospholipids binding proteins. Laboratories diagnosis of APLA can be difficult due to heterogeneity of APLA and a poor standardization of the laboratory tests. The antiphospholipid syndrome (APS) is a form of immune mediated thrombophilia occurring as a recurrent thrombotic event in association with positive laboratory test for antiphospholipid antibodies. The syndrome may be isolated, then defined as primary or secondary when it is associated to different diseases (like malignancies). The thrombotic events associated with APLA can be the first manifestation of malignancy. In patients with malignancy the presence of antiphospholipid antibodies increased the risk of thrombosis. Less than 1% of the patients with APS present a life threatening condition involving multiple organ thrombi and failure named as catastrophic antiphospholipid syndrome.