The purpose of this study is to evaluate the immunohistochemical detection of telomerase enzyme and estrogen receptor (ER) and progesterone receptor (PGR) in gestational trophoblastic neoplasia (GTN) and its clinical significance. Formalin-fixed paraffin blocks for 30 patients (24 with molar pregnancy, 3 with choriocarcinoma, and 3 with placental site trophoblastic tumor) as cases and six products of conception samples from patients with incomplete abortion as controls were included in the study. Immunohistochemical detection of the telomerase catalytic protein and ER and PGR was carried out using streptavidin-biotin-peroxidase method. All control tissues were negative for telomerase and ER expression, while five of six were PGR positive. Significant positive telomerase expression was detected in all gestational trophoblastic tumors (three of six partial moles, 12 of 18 complete moles, three of three choriocarcinomas, and two of three placental site trophoblastic tumors). Nine of 24 molar pregnancies were followed by GTN. Molar pregnancies followed by GTN were associated with higher serum beta-hCG (human chorionic gonadotrophic hormone), larger uterine size for gestational age, negative ER expression, negative PGR expression, and positive telomerase expression. All patients with molar pregnancy with negative telomerase expression (9 of 24) showed spontaneous regression after evacuation. Positive telomerase expression and its immunohistochemical detection are associated with the development of GTN. Negative telomerase expression is highly predictive of postmolar spontaneous regression. Patients with molar pregnancies with negative telomerase expression can be saved the long-term follow-up. ER and PGR expression do not show a significantly different pattern in molar tissues, while negative expression is associated with developing GTN. Cautions on the use of postmolar hormonal contraception may be unjustified.