The article in Nature Communications discusses the validation of a blood-based test for breast cancer detection using DNA methylation in peripheral blood-derived monocytes. The study by Wang et al. reported high accuracy in distinguishing breast cancer cases from controls in their discovery set, but the validation in independent datasets showed limited ability to differentiate cases from controls. The findings highlight the importance of cross-population validation of diagnostic biomarkers before clinical implementation and suggest that inflammation may contribute to the observed signal. The study emphasizes the need for further evaluation and development of accurate diagnostic assays that can be validated across diverse populations.