TCF17, the human homologue of the rat zinc finger gene Kid1, is highly expressed in neurons derived from the retinoic acid-treated human embryonal carcinoma (EC) cell line, NTERA-2. This differentiation-related up-regulation of TCF17 prompted us to investigate its expression during human spermatogenesis and in human testicular germ cell tumors considered to be precursors of EC. Expression of TCF17 increases as spermatogonia differentiate into spermatocytes, indicating that this gene is developmentally regulated during spermatogenesis. TCF17 mRNA levels are high in carcinoma in situ and in seminoma, a tumor derived from carcinoma in situ but still of low-grade malignancy. However, TCF17 expression is decreased in highly malignant EC. The differential regulation of TCF17 during neoplastic germ cell differentiation may be of predictive value in germ cell tumor diagnosis.