Osteonecrosis (ON), or avascular necrosis of bone, has been related to decreased blood flow to the bone. Many local and systemic factors have been implicated in the pathogenesis of ON, involving corticosteroid therapy, systemic lupus erythematosus (SLE), hemoglobinopathies, alcohol abuse, Caisson disease, Gaucher disease, and hypercoagulability states. We describe the case of a previously healthy young male with no history of corticosteroid therapy, who developed ON initially on the femoral head, and later on the humeral head with high levels of anticardiolipin antibodies (aCL), beta-2-glycoprotein 1 antibodies and positive lupus anticoagulant. The association between primary antiphospholipid syndrome (PAPS) and ON is controversial and few cases without other risk factors have been described. A review of ON pathogenesis and its relation with thrombotic microangiopathy because of PAPS is presented.