Background: Li-Fraumeni Syndrome (LFS) is a rare autosomal dominant syndrome associated with germline mutations in TP53 gene. Carriers have a high risk for developing multiple early onset cancers, most commonly breast cancer, sarcomas, brain and adrenocortical carcinomas. Screening strategies for early diagnosis in carriers constitute a major challenge due to the diverse spectrum and ages of onset of tumors. Rapid whole body MRI (RWB–MRI) has been proposed as a screening strategy. In Brazil, there is a high prevalence of a founder mutation (p.R337H TP53) present in 0.3% of the South/Southeastern Brazilian population. Due to genetic modifiers, tumors occur at a later age in p.R337H carriers. Methods: The aim of this study is to evaluate the efficacy of RWB–MRI as a screening strategy in p.R337H TP53 carriers and in classical LFS mutation carriers. A total of 84RWB–MRI were performed in 57 TP53 germline mutation carriers (49 p.R337H TP53), including 27 patients who performed a second exam 12 months after the first RWB–MRI. Results: Two malignant lesions were detected by RWB–MRI: (1) in a 19–year old p.R337H female carrier RWB-MRI demonstrated bilateral renal cortical alterations, confirmed with abdominal MRI which showed an enhancing solid lesion in the right kidney. The lesion was surgically removed and pathological findings confirmed a papillary renal cell carcinoma; (2) in a 30 year old p.R337H female carrier, RWB–MRI detected a solid right breast nodule. Breast MRI detected two solid lesions. Biopsy of each lesion confirmed diagnoses of a ductal carcinoma in situ and benign phyllodes tumor, respectively. Incidental findings were detected in 26/57 patients and further imaging modalities were performed in 9/26 cases which ruled out malignancies and no unnecessary biopsies were performed. No malignant lesions were detected in 8 classical LFS patients. Conclusions: Preliminary results from this study demonstrate the feasibility and effectiveness of RWB–MRI in detecting malignant lesions among 49 p.R337H TP53 mutation carriers.