Ninety-four women with breast cancer who received epirubicin (360 mg/m2) underwent three-dimensional (3D) speckle tracking echocardiography (STE) at baseline, after the completion of two cycles and four cycles of the regimen respectively were enrolled in the study. 3D STE assessment included left ventricular ejection fraction (LVEF), global area strain (GAS), global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS). Meanwhile, serum high-sensitive troponin I (hs‐cTnI) and N-terminal portion pro-natriuretic peptide type B (NT-proBNP) were measured. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as reduction of 3D LVEF > 10% to a value < 54%. CTRCD occurred in 9 (9.6%) patients during anthracycline treatment. The changes in 3D LVEF was not significant after chemotherapy. Values of 3D GLS and 3D GAS showed a significant deterioration during anthracycline treatment (p < 0.001 and p = 0.001, respectively) in all patients. Compared to non-CTRCD patients, the CTRCD patients had significantly reduction in 3D GLS (-15.5±3.2% vs -17.0±2.7%, p<0.001) and 3D GAS (-31.0±3.9% vs -32.3±3.3%, p<0.001) at the end of anthracycline chemotherapy. The optimal cutoff value with -15.5% of 3D GLS had a good discrimination for predicting CTRCD, with 87.5% sensitivity and 74.6% specificity. Spearman correlation analysis showed a moderate negative correlation between 3D GLS and anthracycline doses (r = - 0.54, p < 0.001). 3D GLS could potentially improve the ability for detecting early, subclinical anthracycline-related cardiotoxicity in breast cancer patients.