Purpose. The purpose of this study was to analyze acute locoregional toxicity in patients with breast cancer receiving concurrent pazopanib and RT. Materials and Methods. Patients with breast cancer who received pazopanib in combination with radiation were identified and matched (2 : 1) to patients with breast cancer who did not receive pazopanib by use of chemotherapy, radiation field design, and radiation dose. Toxicity was scored by the Common Terminology Criteria for Adverse Events and statistical analysis was performed. Results. Grade 1 or 2 radiation dermatitis was seen in 100% and 84% of pazopanib and RT patients and matched controls respectively (P = NS). None of the patients receiving pazopanib and RT experienced ≥ grade 3 toxicity within the irradiated volume; three (16%) matched patients experienced a grade 3 skin reaction (P = 0.05). Interestingly, grade 1 or 2 hyperpigmentation was seen in 17% of pazopanib and RT patients and 60% of matched controls (P = 0.005). Conclusion. The addition of concurrent pazopanib and RT when treating the intact breast, chest wall, and associated nodal regions in breast cancer seems to be safe and well tolerated.