Simple SummaryWilms tumor (WT) is a rare form of cancer that typically affects children and is usually confined to the kidneys. Extra-renal Wilms tumor (ERWT) is even rarer and develops in other areas of the body, such as the retroperitoneum and inguinal regions, and occasionally at the level of the spinal cord. We present a case report of a 4-year-old boy diagnosed with spinal ERWT, who was also affected with a spinal dysraphism. Our case-based systematic review of pediatric ERWT showed that a multimodal therapeutic approach (including surgery, chemotherapy, and radiotherapy) is important, but an international standardization of the staging approach and therapeutic protocols is needed to define the best clinical management in these children: indeed, there is a lack of clinical studies focused on pediatric ERWT and international trials are needed to achieve these objectives. Our research emphasizes the importance of timely diagnosis and treatment and, possibly, standardized medical approach, in order to improve the outcome of these very rare pediatric malignancies, whose clinical management is even more problematic in developing countries.AbstractWilms Tumor (WT) is one of the most common renal tumors in the pediatric population. Occasionally, WT can primarily develop outside the kidneys (Extra-Renal Wilms Tumor, ERWT). Most pediatric ERWTs develop in the abdominal cavity and pelvis, whereas the occurrence of this tumor in other extra-renal sites represents a minor part of ERWT cases. In addition to describing a case of spinal ERWT (associated with spinal dysraphism) in a 4-year boy (to add a further clinical experience on this very rare pediatric tumor), we performed a case-based systematic literature review on pediatric ERWT. We retrieved 72 papers providing enough information on the diagnosis, treatment, and outcomes of 98 ERWT pediatric patients. Our research highlighted that a multimodal approach involving both chemotherapy and radiotherapy, after partial or complete tumor resection in most cases, was typically used, but there is no standardized therapeutic approach for this pediatric malignancy. However, this tumor may be potentially treated with a better success rate if the diagnostic confirmation is not delayed, the mass can be totally resected, and an appropriate and, possibly, tailored multimodal treatment can be promptly established. In this regard, an international agreement on a unique staging system for (pediatric) ERWT is definitely needed, as well as the development of international research, which may be able to gather several children diagnosed with ERWT and, possibly, lead to clinical trials which should also include developing countries.