Gestational trophoblastic disease encompasses a spectrum of proliferative disorders, ranging from non-neoplastic to neoplastic, and involves various trophoblastic cell types of the placenta. Laboratory investigations into biomarker expression have helped delineate distinct cellular pathways of differentiation unique to each entity of gestational trophoblastic disease. The most common form, hydatidiform moles, is characterized by the hyperplastic proliferation of cells that mimic the chorionic villous trophoblast. Gestational choriocarcinoma, one of the most malignant human cancers, consists of neoplastic cells that resemble the trophoblast at the primary villous stage of placental formation. In placental site trophoblastic tumors (PSTTs), the neoplastic cells exhibit cytological features akin to the intermediate trophoblast at the implantation site. In contrast, the tumor cells of epithelioid trophoblastic tumor (ETT) resemble the intermediate trophoblast at the chorionic laeve or the chorionic-type intermediate trophoblast. Biologically, the presence of an excessive paternal haploid genome in both complete and partial hydatidiform moles highlights their unique pathogenesis, likely driven by altered genomic imprinting.