Background: There is limited data about the role of isolated central nervous system (CNS) metastasis (mets) in patients with breast cancer (BC), since prior studies evaluated BC patients with CNS plus visceral mets. Furthermore, though Black race is associated with worse BC outcomes, there are few studies on CNS mets that predominantly included racial and ethnic minorities in their cohorts. Our study compares overall survival (OS) in BC patients with CNS involvement with and without visceral mets in an underrepresented patient population. Methods: This is a retrospective case series study. We used Montefiore’s Clinical Looking Glass software to identify patients. Inclusion criteria were females age ≥18 years at our institution with the diagnosis of BC and CNS mets between 3/31/1997 to 3/31/2019. Chart review was conducted to obtain clinical-pathological features, including date of diagnosis, treatment, clinical course, and survival status. Patients with BC and CNS mets were divided into two cohorts, those with additional mets limited to bone and lymph nodes but without further visceral spread (CNS-NV), and those with CNS mets plus visceral mets (CNS-V). Kaplan-Meier methods were used to analyze the median OS. Results: Our study included a high proportion of underrepresented minorities (n=177); 46.3% were Black, 10.7% were White, and 34.5% were Other Race; besides, 28% were Hispanic. Mean age at diagnosis of CNS mets was 58 years (SD = 12.9). 62.1% were estrogen receptor (ER) and/or progesterone receptor (PR) positive, 27.1% were HER2 positive; and 19.8% were ER, PR and HER2 negative. Mean number of chemotherapy and endocrine therapy lines before CNS mets were 2 (IQR = 1-2) and 1 (IQR = 1-2), respectively. CNS-NV and CNS-V cohorts included 35 and 142 patients, respectively. Patients with CNS-NV had longer OS than CNS-V (2118 vs. 1120 days, p=0.02). Further subgroup analysis for group CNS-NV was performed based on treatment modality. In this cohort, OS was not significantly different between patients who did and did not receive chemotherapy (n =35, mean OS 1509 vs. 960 days, p = 0.49). In addition, OS was not significantly different between patients who received and did not receive endocrine therapy (n = 24, mean OS 857 vs. 1394 days, p = 0.4). Finally, OS did not significantly differ between patients who did and did not receive anti HER2 treatment (n = 11, 1753 vs. 849 days, p = 0.15). Conclusions: Minimal research has been conducted on breast cancer patients with CNS mets and distal involvement limited to the bones or lymph nodes. In a heterogenous racial and ethnic population, patients with BC and CNS mets have prolonged OS if the extent of distal involvement is limited to the bones or lymph nodes, compared to those with visceral mets. More research with larger sample sizes is needed to confirm our findings, which may help to de-escalate and tailor treatment for patients with CNS mets.