The antiphospholipid syndrome is a pathological condition characterized by recurrent thrombotic manifestations in venous and/or arterial vascular systems and by peculiar laboratory findings as anticardiolipin antibodies and/or positive lupus anticoagulant. We present a case of massive pedicle thrombosis of a free anterolateral thigh perforator flap used for tongue reconstruction following hemiglossectomy in a patient with antiphospholipid syndrome, which compelled us to an immediate second reconstruction choice with a radial forearm free flap. This case is an example of how this syndrome, especially if unknown before surgery, can influence the outcome of microsurgical transfer of flaps.