Molar pregnancy (complete and partial hydatidiform mole) is a trophoblastic disease of pregnancy characterized by abnormal trophoblast proliferation, hydropic degeneration of villi, and risk of progression to malignant forms such as invasive mole or choriocarcinoma. Estrogen receptor α (ESR1/ERα) plays a key role in normal placental development, facilitating trophoblast differentiation into syncytiotrophoblast and modulating extravillous trophoblast invasion through regulation of matrix metalloproteinases and angiogenic factors. Studies have shown that ESR1 expression is frequently reduced or lost in molar tissues compared with normal pregnancy; ER negativity is associated with higher β-hCG levels, larger uterine size, and an increased risk of progression to gestational trophoblastic neoplasia (GTN). Epigenetic evidence—particularly DNA hypermethylation—has been proposed as a feature of GTD pathogenesis. Genome-wide analyses have shown increased methylation in regulatory regions, transcription start sites, and genes involved in cell-cycle control, steroid biosynthesis, and extracellular matrix pathways. Although ESR1 promoter methylation has not been directly demonstrated in molar pregnancy, comparative studies in other pregnancy disorders (e.g., hypoxia-induced ESR1 suppression or methylation induced by endocrine disruptors) suggest that epigenetic silencing could be a plausible mechanism for ESR1 downregulation. ESR1 downregulation may impair syncytiotrophoblast differentiation, increase cytotrophoblast proliferation, and promote invasive phenotypes that contribute to disease progression. This review summarizes published evidence on ESR1 expression in molar pregnancy and emphasizes the need for targeted studies of ESR1 methylation in GTD cohorts to improve diagnosis and treatment.