Germline mutations in the p53 tumor suppressor gene have been identified in patients with Li-Fraumeni syndrome (LFS) and patients with Li-Fraumeni-like syndrome (LFL). However, to date, germline p53 mutations in patients not fulfilling the criteria of LFS or LFL have been reported only very rarely. In our study, a novel germline c.584T>C (p.Ile195Thr) mutation of the p53 gene was found in a 21-year-old male with a glioblastoma and colon cancer. He had no family history of cancer within second-degree relatives, and loss of the wild-type p53 allele and overexpression of p53 protein were observed in both tumors. Functional analyses revealed transactivation and growth suppressive function activities of the Thr195-type p53 to be impaired. These results suggest germline p53 mutations to possibly be responsible for a subset of young adult patient with multiple malignant tumors, even those not meeting the clinical criteria for LFS or LFL.