Estrogen receptor 1 (ESR1) mutations in breast tumors were first identified nearly 30 years ago. Since then, technology has evolved, as has our understanding of the impact these mutations have on tumor cell physiology. Given the dynamic nature of ESR1 mutation acquisition and enrichment, ctDNA samples appear to be the most robust source for analysis. Droplet Digital PCR (ddPCR) enables rapid, highly sensitive, cost-effective analysis of ctDNA, providing a powerful tool for this critical area of cancer research.