Carcinoma in situ (CIS) is regarded as the precursor lesion of testicular germ cell tumors. In adults CIS cells have also been described within the normal testicular tissue adjacent to mature teratomas with a frequency of 52-88%. These CIS-cells can be identified by immunohistochemical staining for "placental like alkaline phosphatase" (PLAP). In four of eight patients with mature teratomas CIS was identified by immunohistochemistry for "PLAP" in atrophic testicular tubules adjacent to the tumors. In three of these patients cells of CIS were positive for the p53 oncoprotein, indicating a mutational inactivation of the p53 tumor suppressor gene. The malignant potential of mature teratomas, which do occur without histological signs of malignancy, may therefore be associated with the occurrence of CIS within the histologically normal appearing testicular tissue adjacent to the mature tumor. Immunohistochemical positivity for the p53 protein in CIS cells of some patients may indicate that the mutational inactivation of the p53 tumor suppressor gene could be involved early in the development of testicular germ cell tumors.