Background: Next generation sequencing (NGS) of tBx is the basis for precision medicine. Most tBx used for NGS are archival primary tumors, often acquired several years before starting matched treatment. Analysis of ctDNA may better capture the GA landscape of MBC. We aimed to compare the concordance of GA detection by NGS in synchronously acquired tBx and ctDNA in MBC pts. Methods: MiSeq Amplicon-based NGS (panel of 59 cancer-related genes) was performed in both tBx and ctDNA at disease progression. The concordance of GA in tBx vs ctDNA was determined at patient level and at mutation (mut) level in clinically actionable genes (PIK3CA, AKT1, ERBB2, ESR1, PTEN). False negative result in ctDNA (FN-ctDNA) defined as mut detected in tBx but not in ctDNA. Results: 28 pts identified (luminal [lum] 21, HER2+ 5, triple negative 2), median prior lines of therapy 4.5 (0-15). Most pts had visceral metastasis (71%); most biopsies were from non-visceral sites (67%), mainly breast/nodes/skin (59%). In 16 pts (57%), tBx and ctDNA had complete concordant results (4 were wild-type). Concordance was 100% in non-lum and 43% in lum pts (P=0.01). Clinically actionable GA were found in 20/28 (71%) pts. FN-ctDNA rate was 25%; these pts had a trend towards having non-visceral metastasis (OR 3.1, P=0.32). Focusing in clinically actionable genes, concordance was 52% at mut level, being lower for ESR1 mut (Table). Interestingly, ctDNA analysis identified 6 ESR1 mut that were not detected in tissue, including 3 pts with a double ESR1 mut. Conclusions: NGS in ctDNA is feasible and the results may be informative for pts management. Our results suggest that ctDNA may be useful for assessing GA in non-lum MBC and the emergence of ESR1 mut in lum MBC. Double ESR1 mut in ctDNA suggests a mechanism of convergent evolution in acquired resistance to endocrine treatment. Causes of discordant tBx/ctDNA (e.g. tumor burden / heterogeneity, technical issues related to ctDNA isolation / processing), warrant further study in larger datasets.