Certain single nucleotide polymorphisms (SNPs) in genes like p21 or bcl2 increase susceptibility to breast cancer but it has not, until now, been clear whether common polymorphic variants in the same genes also increase risk in Saudi Arabian population. The aim of this study was therefore to determine whether polymorphisms of p21 or Bcl2 might be associated with an increased risk of breast cancer in Saudi women. p21 (rs733590) C/T SNP was not found to be associated with breast cancer pathogenesis. However, we found that a reverse mutation T/C might be linked with breast cancer occurrence. Bcl2 genotypes were marginally associated overall with breast cancer risk. In addition, the alleles of this gene were significantly associated with risk of breast cancer. The allelic frequency of G was higher (0.68) in patients than in healthy women. AA vs. AG+GG genotype [OR=3.56 (1.24-10.68); P=0.008] was the dominant genotype. It is likely that these genes conferring measurably increased risks of breast cancer in our study population.