The aim of this study is to evaluate whether the expression of p27KIP1 (p27) and cyclin E (cE) is related to the development of hydatidiform moles and whether their expressions are associated with prognosis in these lesions. Ten diploid voluntary artificial abortions (ABs), 20 diploid hydropic abortions (HAs), 20 triploid partial moles (PMs), and 44 diploid complete moles (CMs) (including 4 with persistent disease), all of which were in the first trimester, were evaluated by immunohistochemistry of formalin-fixed tissues using monoclonal antibodies against p27 and cE protein. DNA ploidy in all cases was analyzed by flow cytometry. In ABs, nuclear cE was expressed at low (1+) to moderate (2+) levels in cytotrophoblast (CT), intermediate trophoblast (IT) and occasionally in syncytiotrophoblast (ST). In all CMs, cE-positive nuclei of CT were observed at high levels (3+), and (1+) to (2+) levels in clusters of IT. On the other hand, all HAs and PMs showed cE levels comparable to those observed in ABs. There was a significant difference in cyclin E expression in CT between CMs and non CMs, but there was no significant difference of cE levels between CMs with and without persistent disease. In 3 of 10 ABs, nuclear p27 was expressed at (1+) levels in ST. Similar expression was observed in 27 (including 2 invasive lesions) of 44 CMs, 10 of 20 PMs, and 8 of 20 HAs. CT and IT were rarely positive (1+) for p27 in the cases examined. Decidual stromal cells provided a reliable positive internal control for p27 expression. These findings support the hypothesis that trophoblast proliferation is related to the balance between the positive cell cycle factors, such as cE, and the negative cell cycle inhibitors, such as p27. The overexpression of cE in the trophoblastic elements suggests that cE protein expression may be dysregulated in early CMs. Neither cE nor p27 expression is a prognostic indicator in CMs.