Circulating DNA can be isolated from serum of patients with various carcinomas and p53 mutation can be observed in colorectal carcinoma. The aim of this study was to investigate the correlation between p53 mutation in DNA extracted from colorectal carcinoma and that in DNA extracted from serum of patients with colorectal carcinoma. The clinical significance in molecular detection of p53 mutation in serum of patients with colorectal carcinomas was also investigated. DNA was extracted from tumors and non-tumorous colorectal tissues of 46 patients with single sporadic colorectal carcinomas of stage I (n=6), stage II (n=18), stage III (n=15), and stage IV (n=7) according to the TNM classification. Circulating DNA was also extracted from the serum of the 46 patients with colorectal carcinoma and from 7 healthy volunteers for normal control. Mutations of the p53 gene were analyzed using a fluorescence-based polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) method. DNA sequences were determined in DNA fragments with shifted peaks by SSCP methods. Mutations in tumors were found in 22 (48%) of 46 patients, and mutations in serum were found in 3 (14%) of these 22 patients. Of 4 patients with stage IV disease, 3 (75%) had serum p53 mutation and the mutation pattern of these 3 patients was the same in both tumor and serum. No correlation was seen between p53 mutation in serum and the level of serum DNA. There was no significant difference between the presence of p53 mutation in serum and tumor size, depth of invasion, vascular invasion, or lymph node metastasis. However, liver metastasis showed significant difference (p=0.0026). The presence of p53 mutation in serum was associated with a clinically advanced stage accompanied by liver metastasis.