Clinically the anaplastic variant of Wilms' tumor differs from the classical Wilms' tumor by its poor prognosis. To begin to understand and characterize the distinctive biology of this rare form of Wilms' tumor, a study of the histology, ultrastructure, and mRNA expression was performed on the anaplastic tumor and its associated cell line. The anaplastic tumor generated mouse heterotransplants that were readily used to establish epithelial cell cultures. The epithelial cultures, in turn, produced tumors when reinjected into nude mice. Microscopic evaluation revealed that the anaplastic epithelial cells were less differentiated than their epithelial counterpart in classical Wilms' tumors. In general the molecular profile of the anaplastic tumor was more consistent with that of an epithelial-rich classic Wilms' tumor than with the classic triphasic Wilms' tumor. Unlike the classic triphasic Wilms' tumor that contains blastema, stroma, and epithelial tubules, the anaplastic tumor expressed only marginal levels of insulin-like growth factor 2 (IGF-2) mRNA and imperceptible levels of the Wilms' tumor gene (WT-1), Pax-2, and Pax-8 mRNA. In common with the classic Wilms' tumor, the anaplastic variant retained the expression of the N-myc gene while failing to express C-myc. A comparison of cultures derived from an epithelial-rich, classic Wilms' tumor and the anaplastic Wilm's tumor indicated that both lacked IGF-2 and WT-1 mRNA expression. However, the well-differentiated epithelial cell culture derived from the classic Wilms' tumor expressed C-myc, Pax-8, and Pax-2 mRNA, none of which were expressed by the anaplastic epithelial cells. Furthermore, the well-differentiated epithelial cell component failed to express N-myc, which was expressed by both the primary triphasic Wilms' tumor and the anaplastic tumor. Overall, the findings indicate that patterns of gene expression within a single component do not correlate with the aggressive clinical behavior of the anaplastic Wilms' tumor.