We examined five patients with multiple primary cancers who had a history of three different types of primary cancers for germ-line p53 mutations. The germ-line p53 mutation was detected in a patient who conformed to the Li-Fraumeni syndrome, but not in the other four patients. The diagnosis of these four patients did not fall in the category of Li-Fraumeni syndrome. This result indicates that germ-line p53 mutations are uncommon even in patients with triple primary cancers.