Background: CTCs count has been validated as a prognostic biomarker in MBC. In primary breast cancer, diagnostic tools exist to select less aggressive treatments in patients with indolent disease. In the largest CTC analysis to date, we define an indolent subset of patients in MBC, Stage IV _indolent, identified using CTC counts. Methods: We performed a combined pooled analysis of individual patient data in two large cohorts: the European Pooled Analysis Investigators (EPAC) cohort (N = 1,944) and the MD Anderson Cancer Center (MDACC) cohort (N = 492). For all patients (N = 2,436), CTC enumeration was performed using the FDA-approved CellSearch™ (Menarini Silicon Biosystems, LLC) with baseline samples collected before starting a new treatment. Overall survival (OS) data were collected from both cohorts. Patients were stratified based on 5 CTCs/7.5 mL blood (N = 1,336 with < 5 CTC or Stage IV _indolent;≥5 CTC, Stage IV _aggressive). Proportional hazards regression model and stratified log rank tests were performed. Results: For all patients, CTC ≥5 identified patients with a worse outcome (HR 2.43, 95% CI 2.17-2.73, P < 0.0001), while the indolent CTC group had a median OS of 36.3 months (mts). Moreover, for patients with de novo MBC prior to treatment (N = 244), the indolent cohort demonstrated an OS greater than 5.5 years. The Stage IV _indolent disease showed significantly longer OS across all disease subtypes compared to the aggressive cohort, HR+ (44 mts vs. 17.3 mts, P < 0.0001), TNBC (23.8 mts vs. 9.0 mts, P < 0.0001), and HER2+ (36.7 mts vs. 20.4 mts, P < 0.0001). Furthermore, Stage IV _indolent consistently discriminated a less aggressive cohort among subtypes even in the refractory setting. Conclusions: CTC < 5 identifies an indolent subset of MBC, Stage IV _indolent, independent of line of treatment and molecular subtype. A CTCs-based classification of MBC has tremendous implications and practical applications including, considerations for cost-effective single-agent therapy, particularly in the first-line setting, and the availability of a validated stratification tool in prospective efficacy clinical trials.