Beckwith-Wiedemann syndrome is an overgrowth disorder that predisposes to the development of a variety of malignancies including Wilms tumor. Pathologists may suspect the presence of Beckwith-Wiedemann syndrome, which may be clinically subtle, on the basis of the histopathology of the renal parenchyma adjacent to a Wilms tumor. These kidneys typically harbor multiple nephrogenic rests (especially perilobar nephrogenic rests), and their medullas have blunted papillae resulting from excessive fibromyxoid stroma, decreased collecting ducts, and decreased Henle loops. This complex of findings constitutes the so-called Beckwith Medulla. Extensions of this stroma-rich medulla into the cortex results in characteristic dysplastic medullary-ray nodules. Identification of these histologic abnormalities by the pathologist should prompt the clinician to evaluate the child for Beckwith-Wiedemann syndrome. Proper screening of these children can allow for early detection of cancers and treatment while these cancers are curable. © 2006 Sage Publications.