Choriocarcinoma is a unique malignant neoplasm composed of mononuclear cytotrophoblasts and multinucleated syncytiotrophoblasts that produce human chorionic gonadotrophin. Choriocarcinoma can occur after a pregnancy, as a component of germ cell tumors, or in association with a poorly differentiated somatic carcinoma, each with distinct clinical features. Cytogenetic and molecular studies, predominantly on gestational choriocarcinoma, revealed the impact of oncogenes, tumor suppressor genes and imprinting genes on its pathogenesis. The role of stem cells in various types of choriocarcinoma has been studied recently. This review will discuss how such knowledge can enhance our understanding of the pathogenesis of choriocarcinoma, enable exploration of novel anti-choriocarcinoma targeted therapy and possibly improve our insight on embryological and placental development.