We previously demonstrated that human urine contains small, 150 to 250 nucleotide-sized, soluble DNA derived from the circulation, which may be useful in the detection of colorectal cancer. In this report we have determined the stability of DNA in urine and have found that the half-life time interval of this small, fragmented DNA is at least 4 hours post collection. We further compared, in a blinded study, the frequency of detecting mutated K-ras sequence in DNA isolated from plasma and urine derived from individuals who have either a colorectal carcinoma (CRC), or adenomatous polyps that contain a mutation in codon 12 of the K-ras proto-oncogene. There was an 83% concurrence of mutated DNA detected in urine and its corresponding disease tissue from the same individuals, when paired urine and tissue sections from 20 patients with either CRC or adenomatous polyps were analyzed for K-ras mutation. However, only a 56% concurrence was observed when the matched plasma specimens were tested from these 20 patients. These results suggest that urine might be a better resource for detecting K-ras mutation in circulating DNA.