Abstract: Objective To evaluate the role of FLT3 gene mutation in acute promyelocytic leukemia (APL) patients with extramedullary relapse. Methods The blood and bone marrow samples were collected from 2 APL patients with extramedullary relapse and FLT3 gene mutation was detected with these samples. The correlation between FLT3 gene mutation and extramedullary relapse was analyzed. Results A rare point mutation Asn841Gly (A841G) of FLT3-TKD and a novel mutation (c.1209_1210insT/p.K404X) of WT1 were detected in a APL patient who suffered CNS relapse, while a rare point mutation Asp839Gly (D839G) of FLT3-TKD and a novel mutation Arg458Pro (c.1373G>C) of WT1 were found in another APL patient who suffered testicular relapse. Conclusion The rare point mutation of FLT3 as well as the novel mutation of WT1 were found in APL with extramedullary relapse.