Three large studies published in recent issues of Breast Cancer Research reported no overall evidence of an association between the CYP17 5'-untranslated region MspA1 polymorphism and breast cancer. The present commentary briefly highlights a few important observations and discusses some additional approaches to further assessment of associations between CYP17 common variants and breast cancer risk. In particular, the evolution of evidence on breast cancer and the CYP17 MspA1 variant suggests that determination of possible interactions between gene variants postulated to influence risk and nongenetic risk factors would be more efficiently accomplished by pooled analyses, ideally involving all studies of breast cancer, than by attempting to synthesize published information. Furthermore, such analyses would also be relevant to investigation of potential gene-gene interactions between CYP17 and other common variants in genes encoding enzymes that are involved in the synthesis and inactivation of sex steroid hormones, preferably using optimal sets of single nucleotide polymorphisms.