Some previous studies have demonstrated significant results between Ki-ras mutations and tumor stage, survival, and/or other clinical variables, whereas others have not. We therefore evaluated the significance of codons 12 and 13 Ki-ras mutations in a large population-based study of 1413 individuals with colon cancer. Ki-ras mutations were identified in approximately 32% of tumors. Codon 12 mutations were significantly more common in proximal than distal tumors (29.1% versus 20.5%; P < 0.01) and in tumors of advanced stage. Tumors from men were more likely to have transition mutations and codon 12 G-->A mutations. After adjusting for age and stage, the codon 13 G–>A mutation was associated with a 40% (95% confidence interval, 0.95-2.0) increase in short-term mortality from colon cancer. In conclusion, this population-based study demonstrates important relationships between Ki-ras mutations and stage, survival, tumor location, and gender.