Background:Thromboembolism is a well-recognized complication in children with cancer and associated with chronic morbidity, delay of treatment, adverse events associated with anticoagulation and rarely mortality ,so we aimed to study the relation between susceptibility to prothrombotic defects and pediatric cancers.Methods: this case control study included 50 patients aged from 1-14 years categorized into two groups: 25 children with newly diagnosed cancer as case group and 25 completely healthy, age and sex matched children as control group.All subjects were tested for prothrombin gene mutation by Polymerase chain reaction and evaluated for other clinical and laboratory risk factors for TE in children with cancer including age ,sex,blood group,cancer type ,chemotherapy received,central venous catheter insertion,past history of TE,family history of TE,clinical presentation, level of serum protein C,serum protein S, D-Dimer،(INR) then all cases were followed for 3 months after starting chemotherapy.Results:Out of 25 pediatric patients with cancer, 28% had heterozygous prothrombin gene mutation ,while 16% of control group had the same mutation.Also 4% of studied patients developed TE.There was non-significant difference between studied groups regarding prothrombin gene mutation and there was significant difference between them according to PS,PC,D-dimer, prothrombin time and platelets counts.There were non-significant relation between prothrombin gene mutation and either gender,age,family,past history of TE or cancer type and development of thromboembolism. Conclusion:There was a relationship between the age,presence of family or past history of TE,non O blood group,exposure to steroids and asparginase,presence of CVC,prothrombin gene mutation as strong risk factors for TE and pediatric cancer.Keywords: Thromboembolism,Prothrombin gene mutation,Pediatric cancer.