The few cases of antiphospholipid syndrome that have been reported in neonates are believed to have resulted from a transplacental transfer of antiphospholipid antibodies. Here we report on a boy with a neonatal stroke revealing a de novo primary antiphospholipid, the mother being free of antiphospholipid antibodies. Other thrombosis risk factors included primiparity, gestational diabetes, macrosomia, polyglobulia, and lipoprotein(a) >30 mg/dL. Anti-cardiolipin and anti-β(2)-glycoprotein I persisted more than 2 years. Under aspirin therapy, the child did not exhibit recurrence of thrombotic events or symptoms of autoimmunity after a follow-up of 3 years. Our case indicates that clinicians should consider a second retesting for anticardiolipin antibodies and anti-β(2)-glycoprotein I antibodies, even when children and mother neonatal tests are negative.