Smith et al (2002) investigated K-Ras, p53 and APC in 106 cases and 10% CRC were reported free of molecular abnormalities. Lee et al (2004) examined promoter methylation of 12 different genes in 149 CRCs and found that 9% were unmethylated. Chiang et al (2004) also demonstrated that the three key mutations (APC, K-Ras and p53) are rarely coincidental in 122 sporadic CRCs. This evidence concerns the gene APC and colorectal carcinoma.