In this case-control study based on 250 women with breast cancer and 250 age-matched controls, we sought to evaluate the role of four polymorphic variants in the CYP1A1 gene in breast cancer susceptibility in Nigerian women. Heterozygosity for the CYP1A1 M1 genotype (CYP1A1 M1 [T/C]) was associated with a 21% reduced risk of breast cancer (OR = 0.79, 95% CI 0.46-1.40) while homozygosity for the genotype (CYP1A1 M1 [C/C]) conferred a non-significant 9% reduced risk of breast cancer. These risk profiles were not significantly altered in subgroup analysis by menopausal status. While heterozygosity for the CYP1A1 M3 genotype (T/C) conferred a non-significant 24% reduced risk of breast cancer (OR = 0.76, 95% CI 0.47-1.22), homozygosity for the variant was associated a non-significant 1.95-fold increased risk of breast cancer (OR = 1.95, 95% CI 0.24-6.01). Subgroup analysis showed a non-significant 11% reduced risk in premenopausal heterozygous carriers (OR = 0.89, 95% CI 0.45-1.44) and a non-significant 6% increased risk of postmenopausal breast cancer for carriers of the CYP1A1 M3 (T/C) genotype. The CYP1A1 M2 (isoleucine to valine) polymorphism in exon 7 and CYP1A1 M4 (threonine to asparagine) variant in codon 461 of the CYP1A1 gene were found to be very rare in our study subjects. This study has shown that while the CYP1A1 M1 polymorphism conferred reduced risk of breast cancer, homozygosity for the CYP1A1 M3 (C/C) was associated with increased risk of breast cancer although these risks did not attain statistical significance.