Both two-dimensional (2D) and three-dimensional (3D) echocardiography can be used in the early diagnosis of myocardial toxicity in patients with anthracycline chemotherapy. However, there are few studies on the detection of early myocardial damage in specific regions. This study compared the role and significance of 2D strain and 3D strain in discovering early segmental dysfunction. We prospectively studied 56 breast cancer patients who received anthracycline therapy. The mean age of patients was 47.6 ± 8.1 years. They all received 4-6 cycles of chemotherapy. Before chemotherapy and after every two cycles, patients underwent standard echo, 2D and 3D speckle-tracking echocardiography (STE) and real-time three-dimensional echocardiography (RT-3DE). Compared with the baseline value (T0), 3D GLS was significantly reduced after two cycles (T2) (P<0.05), after four cycles (T4) 3D GCS was significantly reduced (P<0.05), after six cycles (T6) 2D derived EF, 2D GLS, E/e’ ratio, Fractional shortening (FS), 3D derived EF, 3D GAS, GRS were considerably decreased (P<0.05). The area supplying blood from the anterior descending branch of the left coronary artery was the most susceptible to chemotherapy, and 3D GLS was found earlier than 2D GLS which was decreased considerably after two cycles (P<0.05). In anthracycline chemotherapy patients, some regions of early myocardial dysfunction may be more easily involved, through the evaluation of 2D and 3D echocardiography, 3D speckle tracking echocardiography may be more able to identify the involved segments of myocardium early. Moreover, the apical segments of the left ventricle seem to be more susceptible to cardiotoxicity.