Testing the statistical associations between microarray-based gene expression signatures and patient outcome has become a popular approach to infer biological and clinical significance of laboratory observations. Venet and colleagues recently demonstrated that the majority of randomly generated gene signatures are significantly associated with outcome of breast cancer patients, and that this association stems from the fact that a large proportion of the transcriptome is significantly correlated with proliferation, a strong predictor of outcome in breast cancer patients. These findings demonstrate that a statistical association between a gene signature and disease outcome does not necessarily imply biological significance.