Solitary autonomous thyroid tumors are an unusual cause of hyperthyroidism, particularly in childhood. We describe the youngest individual so far reported with this condition, a 22 month child with a large hyperfunctioning thyroid nodule who became overtly hyperthyroid after iodinated contrast administration. The histology of the nodule was compatible with follicular cell hyperplasia. These tumors are often called toxic adenomas, although there is no solid evidence that they are true neoplasms. We examined the clonal composition of the child's thyroid tumor by X-chromosome inactivation analysis, taking advantage of a polymorphism in the X-chromosome gene phosphoglycerate kinase. The tumor consisted of an even mixture of cells containing activated paternal and maternal PGK alleles, indicating that the tumor was polyclonal. Furthermore, the nodule had no structural rearrangements or activating point mutations of ras oncogenes, which are found in up to 50% of solitary monoclonal follicular adenomas. Solitary hot nodules may at least in some cases be secondary to hyperplasia, and not to clonal expansion of an abnormal, mutated cell. This may also explain the relatively low frequency of malignant transformation observed in hyperfunctioning thyroid tumors.