Background: Patients with de novo metastatic breast cancer (dMBC) have superior median overall survival (mOS) compared to recurrent metastatic breast cancer (rMBC). Whether patient characteristics, prior treatment, tumor stage and innate biological differences contribute to this observation is unknown. Methods: Clinical and pathological data from patients diagnosed with MBC from 2011 to 2017 at the University of North Carolina (UNC) was obtained from the prospective UNC Metastatic Breast Cancer Clinical Database (223 dMBC, 607 rMBC). Only patients with known survival status were included. Subtype was determined by hormone receptor (HR) and HER2 staining of the primary tumor. Pathologic staging results were used when available, otherwise clinical staging was used. Patient and tumor characteristics were compared using chi-square testing, and survival outcomes by Cox proportional hazards modeling. Results: 26.9% of patients with MBC presented with dMBC, with significant variation in the ratio of dMBC to rMBC across subtypes. In particular, there were more cases of HER2+ dMBC than rMBC (26.9% vs 14.0%) and fewer cases of triple negative dMBC (20.6% vs 35.3%)(p-value < 0.001). Nearly half of all cases of HR-/HER2+ MBC were de novo (48.2%). dMBC was significantly associated with older age (p = 0.002), lower grade (p = 0.027), higher T and N stage (p < 0.001) and African American race (30% vs 22%, p = 0.022). There was no significant difference in proportion of patients with visceral metastatic disease or in number of metastatic sites at diagnosis. Median follow up was 39 months in both cohorts. mOS was 12 months greater in dMBC than rMBC (34m vs 22m, p < 0.001). These differences were significant across all subtypes except HR+/HER2+. The difference in mOS between dMBC and rMBC was greatest in the HR-/HER2+ subgroup (45m vs 15m, p = 0.006). In multivariable analysis, dMBC remained associated with improved survival (adjusted hazard ratio 0.59, p < 0.001) independent of variables including age, race, subtype, grade and number of metastatic sites at diagnosis. Conclusions: Patients with dMBC have significantly better prognosis than those with rMBC. This improved outcome is in part due to subtype variation, with more triple negative and fewer HER2+ tumors in rMBC, however these differences largely remained when stratified by subtype. In multivariable analysis, de novo presentation of MBC remained an independently significant contributor to longer survival. Further investigation should focus on biologic differences between dMBC and rMBC.