Radiotherapy (RT) in the thoracic region is associated with an increased risk of late cardiovascular morbidity and mortality. Ultrasonic tissue characterisation (UTC) is a non-invasive method of identifying changes in myocardial tissue, such as increased fibrosis. The aim of this study was to assess whether UTC can detect early RT-induced myocardial alterations. Seventy-eight eligible patients with early stage breast cancer were evaluated before and immediately after RT. Twenty patients had right-sided and 58 left-sided breast cancer. None received chemotherapy. A comprehensive echocardiographic examination included 3D measurements and UTC of the right ventricular (RV) free wall, ventricular septum and left ventricular (LV) posterior wall. Integrated backscatter calibration was done for the pericardium (cpIBS) and LV cavity (ccIBS). RT for left-sided breast cancer was associated with increased echodensity in the UTC analysis. RV free wall and ventricular septum cpIBS increased from −15.0 ± 7.3 to −13.7 ± 7.9 dB (p = 0.079) and from −18.2 ± 5.1 to -16.0 ± 6.4 dB (p = 0.002), respectively. Likewise, ccIBS in the RV free wall increased from 20.4 ± 5.9 to 22.1 ± 5.6 dB (p = 0.046), and in the LV septum from 17.3 ± 5.2 to 19.8 ± 5.5 dB (p < 0.001). In 3D echocardiography, LV mass increased from 102 ± 18 to 107 ± 18 g (p = 0.005). Patients receiving RT for right-sided breast cancer did not display these changes. Left-sided RT increased myocardial echodensity, particularly in the structures receiving the highest radiation dose. Considering the progressive nature of the RT induced damage, these early changes may help us with individual risk stratification and serve as a tool for screening.