The complete mole is androgenetic in origin. The vast majority of complete moles result from the fertilization of an egg devoid of nuclei (an empty egg) by a haploid spermatozoon. Fertilization of an empty egg by two spermatozoa is responsible for a rare class of complete mole. The genome of choriocarcinoma should reflect that of the pregnancy from which the tumour arose. Thus, the predominant association of complete mole with choriocarcinoma suggests that the molecular events for the formation of a complete mole and the malignant conversion of trophoblasts are related. The monoallelic contribution shown in complete mole would render a certain gene susceptible to functional inactivation by ‘one-hit’ kinetics. Alternatively, uniparental transmission of genes that are subject to parental imprinting in humans would impair their regulation. Loss of NECC1 expression, and enhanced H19 expression in choriocarcinoma would reflect the genetic features exhibited by the putative forerunner, complete mole. In addition, alterations in gene expression profiles accompanied by malignant conversion of trophoblasts would facilitate chorio-carcinogenesis from complete mole. In future, identification of molecular targets down- or up-regulated in choriocarcinoma will provide us the management tools for gestational trophoblastic diseases.