Recent studies have implicated cyclin D1 G870A single-nucleotide polymorphism (SNP) in susceptibility to and early onset of colorectal cancers (CRC). We investigated the role of cyclin D1 G870A SNP in Singapore CRC patients without dominant family history by genotyping 254 patients and 101 controls. The risk of cancer for AA individuals was less than half that of GG individuals (odds ratio (OR) 0.41; 95% confidence interval (CI) 0.18-0.96). Furthermore, AA and AG patients whose tumours were Dukes C and D (OR 0.38; 95% CI 0.17-0.83), poorly differentiated (OR 0.28; 95% CI 0.09-0.84) and left-sided (OR 0.45; 95% CI 0.21-0.98) were associated with significantly lower risk than GG patients. Young (aged 50 years or less) GG patients had a 5-year lower mean age at onset than AA/AG patients (P=0.02). Young male GG patients had worse disease-specific survival than AA/AG patients (P=0.002). Thus, contrary to Caucasians, the GG (rather than AA) genotype is associated with increased susceptibility and advanced CRC in Singapore patients, suggesting a more complex relationship between the SNP and CRC risk, possibly modulated by population differences.