Acquired FXIII deficiency has been described in association with malignancies or autoimmune disorders. We report two cases of acquired FXIII deficiency associated with hematologic malignancies. The first patient is a 60-year-old male with CMML who presented 4 weeks after confirming his diagnosis with non-traumatic anterior abdominal wall hematoma. Workup revealed FXIII deficiency. He was treated with FXIII replacement and other supportive measures. The hematoma resolved and patient was maintained on factor replacement. Unfortunately, his disease transformed to AML and he succumbed to death after starting AML therapy despite achieving complete remission. The second patient is a 24-year-old male patient post haploidentical transplant for intermediate risk AML. He developed hemorrhagic cystitis day 36 post-transplant and non-traumatic subdural hematoma on day 60 post-transplant. Workup revealed FXIII deficiency. He was treated with factor replacement and the subdural hematoma resolved with improvement of the hemorrhagic cystitis. Both patients had RUNX1 mutation which regulates expression of F13A1 in megakaryocyte this can decreased platelet expression of F13A1 in patient with RUNX1 haplodeficiency which lead to platelet dysfunction. FXIII deficiency should be considered for patient with unexplained bleeding with normal routine workup.