We investigated the expression of the SpanX protein family in cells of normal testes and in testicular germ cell tumours, mainly seminomas and embryonal carcinomas, using an immunohistochemical approach. Most of the normal germ cells, belonging to spermatogonial and primary spermatocytic classes, showed a strong nuclear positivity. In contrast, post-meiotic germ cells showed diffused cytoplasmic and sometimes also perinuclear localization of the signal. The vast majority of cells were also positive in eight seminomas, six embryonal cell carcinomas and one teratocarcinoma. In all seminomas, nuclei were either exclusively or preferentially labelled; whereas, the nuclear signal intensity decreased in parallel with the appearance of some cytoplasmic staining in embryonal carcinomas. In conclusion, these data suggest that the SpanX protein family is not exclusively expressed post-meiotically and that seminomas and embryonal carcinomas may originate from SpanX-positive carcinoma-in-situ cell.