Background: Clinicians increasingly order next generation sequencing (NGS) of tissue or liquid (ctDNA) biopsies from patients with metastatic breast cancer. Although some genetic information is clinically actionable, some, particularly non-ERBB2 gene amplifications, is not. We reviewed NGS data from a real-world cohort of metastatic breast cancer patients to evaluate the prevalence of somatic abnormalities using commercial NGS technology. Methods: We evaluated Foundation One NGS data from 44 tissue and 17 liquid biopsies from patients seen in a medical oncology practice between 2016 and 2022. We used KM Plotter to measure overall survival in early-stage patients by relative gene expression. Results: 76% of patients had ductal and 24% had lobular carcinomas. 59% of patients had luminal (ER-positive) and 32% of patients had basal breast cancer (ER-negative). Only 9% of patients had HER2-positive disease. 48% of the tumors had a p53 abnormality, either a point (59%) or frameshift mutation (36%). 50% tumors had a somatic mutation in a tumor suppressor gene such as PTEN, RB or APC. One patient had a germline BRCA1 mutation and 5 patients had germline BRCA2 mutations. 39% of patients carried a somatic mutation in PIK3CA, predominantly H1047R (45%) in the kinase domain or E545X (20%) in the helicase domain. KM plotter showed worse OS in early-stage patients with low p53 gene expression or high PIK3CA expression. 10/11 patients with lobular carcinoma had somatic mutations in CDH1, 70% of which were frameshift mutations. 8/27 patients with luminal cancer had an ESR1 mutation, predominantly Y537 or D538. 9 patients, predominantly luminal, had amplifications of the 11q13 (CCND1). 7 patients had amplifications of 8q24 (MYC). 20q13 (AURKA) amplifications were only seen in luminal cancers. 12p13 (CCND2) amplifications were only seen in basal cancers. 27% of lobular cancers (vs. 6-17% of ductal cancers) demonstrated amplification of the 11q13, 8q24 and/or 8p11 amplicons. 20q13 and 12p13 amplifications were only seen in ductal cancers. Liquid biopsies were more likely to detect point mutations than tissue biopsies. p53 mutations were seen in 65% of liquid vs. 48% of tissue biopsies. 47% of liquid biopsies showed two p53 mutations. PIK3CA mutations were seen in 71% of liquid vs. 39% of tissue biopsies. 18% of liquid biopsies showed two PIK3CA mutations. 93% of basal cancers had at least one p53 mutation. 44% of luminal cancers had a PIK3CA mutation. ESR1, GATA3 and AKT1 mutations were only seen in luminal cancers. While ESR1 mutations were seen in ductal and lobular cancers, GATA3 and AKT1 mutations were only seen in ductal cancers. Conclusions: Commercial NGS testing of a real-world cohort yields actionable mutations that can impact clinical management and outcome of metastatic breast cancer patients. NGS testing demonstrates the range of gene amplifications and corresponds closely with what has been reported in the published literature.