Background: HER2-low status in mBC is predictive of benefit to trastuzumab deruxutan, but whether it is biologically distinct from HER2-neg disease is unclear. To better understand the prognostic significance of HER2-low status, we assessed patterns of metastases and real world overall survival (rwOS) by HER2 and HR status. Methods: Pts with mBC diagnosis from 1/1/2011 to 5/31/2022 were selected from the nationwide deidentified Flatiron Health electronic health record (EHR)-derived database. HER2 and HR status was derived from human abstraction (IHC 0-1+/2+/3+, FISH pos/neg, ER/PR) and machine learning-extraction (to classify IHC 0/1+). HER2 and HR tests prior and up to 60 days after metastatic diagnosis date (met Dx date) were included, results closest to met Dx date were used. Sites of metastasis (SOM) were grouped into mutually exclusive groups: brain, non-visceral (bone, skin, lymph node) and visceral (liver, lung, etc). Metastatic patterns stratified by HR/HER2 status were compared using chi-square tests. The association between HER2 status and rwOS, stratified by HR status, was evaluated using Cox models adjusted for age, race/ethnicity, practice, SOM, SES, and stage. rwOS stratified by HR/HER2 status and SOM were estimated via KM analysis. Results: Among 22,932 pts with mBC, HER2-low prevalence was 49%. HER2-low mBC was more likely to be HR+ than HER2-neg or HER2+ (84%, vs 70% and 65%; p<0.01). Pts with HER2-low and HER2-neg mBC had similar SOM overall, distinct from HER2+. For example, among HR+ pts, HER2-low and HER2-neg pts were less likely than HER2+ pts to have brain (4% and 4% vs 10%; p<0.01) or visceral metastases (51%, 50% vs 58%; p<0.01) but more likely to have non-visceral metastases (45% and 46% vs 32%; p<0.01). Compared to HER2-low pts, HER2-neg pts had similar rwOS if HR+ (hazard ratio 1.02, 95% CI 0.98-1.08) and slightly worse if HR-neg (hazard ratio 1.18, 95% CI 1.03-1.21). rwOS varied by HR/HER2 status and SOM. Conclusions: Our findings indicate that HER2-low mBC has biologic similarities to HER2-neg mBC. While slight differences were observed between HER2-neg and HER2-low pts in the HR-neg subgroup, overall rwOS differences were associated more strongly with HER2+ status, HR+ status, and metastatic pattern, indicating that HER2-low status may be more informative as a predictive rather than a prognostic biomarker.