Recent ultrastructural, cytogenetic, and ploidy analyses indicate that seminoma acts as a precursor from which other forms of testicular germ cell tumor may originate. Ten cases of primary or metastatic testicular germ cell tumors were investigated that showed possible transformation of seminoma to yolk sac tumor. Such transformation was identified in six cases in which foci of abrupt change from seminoma to various patterns of yolk sac tumor occurred, often at the periphery of otherwise pure lobules of seminoma. Immunostains for cytokeratins, placental-like alkaline phosphatase, and alpha-fetoprotein demonstrated the expected changes in reactivity at the foci of such transformation. Four additional cases were regarded as either seminomas with artifactual microcystic change or the close association of seminoma and yolk sac tumor but lacking evidence for transformation. These data support the theory that seminoma is not an "endpoint" neoplasm but may serve a precursor role in the progression to nonseminomatous germ cell tumors.