All-trans retinoic acid (ATRA) is currently recommended as standard treatment for acute promyelocytic leukaemia (APL). However, there has been increasing concern that ATRA is associated with unusual sites of relapse. We present three cases of APL previously treated with ATRA who ultimately relapsed within the central nervous system (CNS) and hypothesize that, by up-regulating intercellular adhesion molecules, ATRA may facilitate the passage of malignant promyelocytes across the blood-brain barrier.