Several recent epidemiological studies examined the association of N-acetyltransferase (NAT) 1 and 2 genotypes and breast cancer risk. Taken together, these studies do not support a strong role for the most common NAT alleles in etiology of breast cancer. Only one study estimated odds ratios (ORs) for the relatively rare NAT1*11 allele: a strong positive association for the NAT1*11 allele and breast cancer was reported, as well as strong combined effects for NAT1*11-containing genotypes and two environmental factors, smoking and red meat consumption. To further address the association of NAT1*11 and breast cancer, an analysis was performed using previously collected data from the Carolina Breast Cancer Study, a population-based, case-control study conducted in North Carolina. The OR for NAT1*11-containing genotypes and breast cancer was 0.5 (95% confidence interval, 0.2-1.3) among white women; ORs were not calculated among African Americans because only one participant exhibited the NAT1*11 allele. There was no evidence for combined effects of NAT1*11 and smoking. Unfortunately, the results of both studies of NAT1*11 are imprecise and lack sufficient statistical power to address fully the potential contribution of NAT1*11 to breast cancer. These results illustrate that the limitations imposed by sample size, as well as incomplete knowledge of biological function, need to be considered when planning and interpreting studies of genetic polymorphisms and environmental exposures.