CD143 (angiotensin I-converting enzyme) occurs in two isoforms: a testicular form (tCD143) expressed during spermatogenesis, and a somatic form (sCD143) generally found in certain other cell types. To study these isoforms in normal and neoplastic germ cells of humans, we analyzed a broad collective of different testicular germ cell tumors (GCTs) of adults, adjacent intratubular germ cell neoplasms (IGCNs), and testicular tissues representing the regular germ cell development. Different techniques were employed on fresh frozen and formalin-fixed, paraffin-embedded tissues: CD143-mRNAs were analyzed by RT-PCR on selected cells after UV-laser-assisted cell picking and by in-situ hybridization using cRNA probes; the proteins were analyzed by semi-quantitative immunohistochemistry using monoclonal antibodies to CD143, and to PLAP/GCAP as controls. In contrast to normal germ cells bearing only tCD143 during spermiogenesis, both mRNA and protein of sCD143 were detected in neoplastic cells of all IGCNs and in the majority of seminomas. sCD143 expression also was found during testicular development, but was differently regulated in fetal germ cells and in GCTs compared with PLAP/GCAP. Thus, our findings (i) demonstrate profound changes in the expression of both CD143 isoforms during regular germ cell development and maturation, (ii) suspect sCD143 being involved in the regulation of germinal stem cell proliferation, (iii) are in agreement with the concept of an 'embryonic state' of neoplastic germ cells, (iv) indicate a close molecular relationship between IGCN and seminoma and, finally, (v) suggest sCD143 as an appropriate marker in the diagnosis of seminomas in addition to PIAP/GCAP.