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Human germ cell tumours (GCTs) have long fascinated investigators for a number of reasons. Being pluripotential tumours, they can differentiate into both extra-embryonic and embryonic (somatic) tissues. However, it has never been shown convincingly that, in humans, these tumours are truly totipotent and can also give rise to the germ lineage, the third major differentiation lineage occurring early during embryonic life. Using a number of newly available, distinct, immunohistochemical markers, such as OCT3/4, VASA and TSPY, the occurrence of germ cells was investigated in a number of germ cell tumours. Development of germ cells was identified in three independent non-seminomas, including two pure yolk sac tumours and one mixed tumour composed of yolk sac tumour and immature teratoma. Our finding indicates a previously unknown totipotent potential of human GCTs and raises the question of whether, under certain culture conditions, primordial germ cells could be derived from human GCT cell lines. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.