Alkaline phosphatase is a useful and reliable marker of germ cell neoplasia that has been almost completely overlooked in the recent medical literature and in the practice of surgical pathology. Its presence in immature germ cells and in germ cell cancers was noted as early as 1953, but a systematic study of its use in the diagnosis and classification of germ cell tumors has not appeared in the literature. Using a recently developed plastic embedding technique combined with enzyme histochemistry, a large series of germ cell tumors and gonadal specimens were examined for the presence of alkaline phosphatase. The neoplastic germ cells in all cases of seminoma and embryonal carcinoma showed strong plasma membrane positivity for alkaline phosphatase. Choriocarcinomas (gestational and nongestational) and mature teratomas were negative. These findings suggest that the alkaline phosphatase reaction is a useful adjunct in the diagnosis of germ cell cancers.