Precursor lesions of spontaneous nephroblastoma (NB) in rats are here characterized for the first time, with a description of the progression of the tumor in prenatal, postnatal, and adult Sprague-Dawley rats (Upj:TUC[SD]spf.nb), which are genetically predisposed to the tumor. NB in the rat starts as a focal or multifocal interstitial accumulation of intensely basophilic immature (blastema) cells, invariably located in the deep renal cortex. Precursor lesions of NB (designated intralobar nephroblastematosis) and the early tumor do not overtly disrupt the overall structural organization and integrity of the kidney. However, with increasing size and neoplastic transformation, these lesions trap, compress, and displace/replace the existing renal tubules. Nephroblastematous foci occurred in one or both kidneys in tumor-bearing or non-tumor-bearing kidneys and in young and old rats. Like the precursor lesions, the early tumors in rats as young as 6 weeks of age were located in the inner cortex. Well-developed NB was comprised of blastema cells arranged in dense sheets or in ductular structures surrounded by mantles of blastema cells supported by varying amounts of fibromatous stroma. The stroma in one rat was hemangiosarcomatous (triphasic Wilms' tumor). Tumor cells were slightly pleomorphic and had varying amounts of granular cytoplasm with sparse organelles and showed junctional complexes and basal laminae whose frequency apparently depended upon whether the blastema cell tended to differentiate to epithelial or mesenchymal cells. NB in the rat was morphologically similar to immature pre- and postnatal kidneys, regardless of whether it occurred in young or old rats. The deep cortical location and interstitial infiltrative characteristics of precursor lesions of NB in the rat were analogous to intralobar nephrogenic rests, a variant of the precursor to Wilms' tumor in children.