Primary intracranial germ cell tumors (GCTs) comprise 3.1% of all brain tumors and 13.6% of those in patients younger than 15 years of age in Japan. They are classified into five basic histological types: germinoma, teratoma, choriocarcinoma, yolk sac tumor, and embryonal carcinoma; or into mixed tumor types when they consist of two or more components. Radiation therapy with or without chemotherapy has proven effective in the treatment of germinoma, whereas there is a poor prognosis for choriocarcinoma, yolk sac tumor, embryonal carcinoma, and mixed tumors having components of the group of malignant intracranial GCTs. The underlying mechanisms for such different responses to radio- and chemotherapies of intracranial GCTs remain unknown. In this study, the authors analyzed the expression of p53 and p21(WAF1/Cip1) proteins by immunohistochemical analysis in 35 intracranial GCTs. Expression of p53 protein was observed in 33 (94%) of 35 intracranial GCTs. Expression of p21(WAF1/Cip1) was detected in seven (20%) of 35 intracranial GCTs. None of the 15 germinomas was immunoreactive for p21(WAF1/Cip1) protein, whereas in a group of malignant intracranial GCTs, four (80%) of five cases showed immunoreactivity for p21(WAF1/Cip1) protein. Analysis of the data suggests that overexpression of p21(WAF1/Cip1) in intracranial GCTs may correlate with decreased sensitivity to radio- and chemotherapy and suggest a poor prognosis.