Mutations in the PIK3CA gene are common in breast cancer and represent a clinically useful therapeutic target. Several larger, population-based studies have shown a positive prognostic significance associated with these mutations. This study aims to further identify characteristics of patients harboring PIK3CA mutations while evaluating the clinical impact of genomic testing for these mutations. Tumors from 312 patients at Vanderbilt-Ingram Cancer Center were analyzed for PIK3CA mutations using a multiplex screening assay (SNaPshot). Mutation rates, receptor status, histopathologic characteristics, and time to recurrence were assessed. The number of patients participating in clinical trials, specifically trials relating to the PIK3CA mutation, was examined. Statistically significant differences between wild-type and mutated tumors were determined using the Wilcoxon, Pearson, and Fischer exact tests. The PIK3CA mutation was found in 25 % of tumors tested. Patients with PIK3CA mutations were significantly more likely to express hormone receptors, be of lower combined histological grade, and have a reduced time to recurrence. Patients found to have a PIK3CA mutation were significantly more likely to enter a PIK3CA-specific clinical trial. In addition to confirming previously established positive prognostic characteristics of tumors harboring PIK3CA mutations, this study demonstrates the feasibility and utility of mutation profiling in a clinical setting. PIK3CA mutation testing impacted treatment and resulted in more patients entering mutation-specific clinical trials.