It is paradoxical that such a presumably quiescent tissue as myometrium, so sheltered from carcinogen exposure, has more neoplasms than any other internal tissue and that, in contrast to cervix and endometrium, pathology textbooks recognize no precursor. Although myometrial dysplasia has been described, it is rare. Myometrial hyperplasia (MMH) is a common structural variation characterized by irregular zones of increased myometrial cellularity, with increased nucleus-cell ratios; but to date, there has been only anecdotal evidence that it may give rise to myomas. We studied the relationship of seedling myomas to MMH in 50 consecutive hysterectomies and found that most seedling myomas (44/63, 70%) arose in MMH--35 in inframucosal MMH, 3 in subserosal MMH, and 6 from intramural MMH. Some seedling myomas were incompletely circumscribed, seeming to arise not only in but also from MMH. We suggest that even seedlings in normal myometrium may arise not from normal myometrial smooth muscle cells but rather from myometaplasia in intramural stromal emboli, with hyperplastic and then neoplastic transformation. These findings may explain the high frequency and multiplicity of uterine leiomyomas. Frequent mucosal injury with stromal repair reactions may release growth factors that promote the high frequency and multiplicity of uterine leiomyomas.