Background: The choice between hormonal therapies and chemotherapy is a frequent decision in the care of mBCa pts. We previously developed quantitative measures of phenotypic CTC heterogeneity in mCRPC, and found higher heterogeneity was associated with better survival on chemotherapy vs. targeted hormonal therapies, and the reverse was true in low heterogeneity patients (Scher et al. 2017 Cancer Research). We sought to apply our previous heterogeneity quantitation methodologies to a cohort of mBCa patient CTCs to ascertain feasibility in mBCa. Methods: 295 blood samples from mBCa patients were processed for CTC analysis utilizing the Epic Sciences platform. Following enumeration, multi-dimensional phenotypic characterization analysis was performed utilizing protein expression and digital pathology features. Features from each CTC (3994 CTCs from 165 pts, 84 HR+, 19 Her2+, 8 HR+/Her2+, 54 TNBC) were compared by unsupervised clustering, Shannon Index and intra-patient variance analyses to assess the intra-patient heterogeneity among mBCa CTC phenotypes. Results: CTCs were detected in 76.9% (227/295) of mBCa patients (med = 2.4 CTC/mL, Range 0 - 747). Distinct CTC phenotypes were identified and associated with mBCa subtypes. Subset of CTCs from TNBC pts had larger nuclear area and higher CK expression vs. other subtypes. In addition, we observed marked differences in heterogeneity in CTCs across patients, with some patients having relative uniform CTC profiles, and others with high phenotypic diversity. mBCa subtypes had similar intra-patient heterogeneity level. Conclusions: Distinct CTC phenotypes can be visualized reproducibly across patients and associated with specific mBCa subtypes. Our analysis revealed significant heterogeneity between individual CTCs both between and within patients. Identification of patients with high heterogeneity may help to find patients unlikely to respond to targeted therapies. Studies to link heterogeneity to therapeutic efficacy and pt outcome are ongoing.