Objective: To explore the utility of circulating tumor DNA detection in early breast cancer by using next-generation sequencing. Methods: This exploratory study of circulating tumor DNA detection is for early invasive breast cancer patients treated in Breast Disease Center, Peking University First Hospital from December 2015 to July 2016. Plasma samples were collected and were used to isolate plasma cell-free DNA.Exons or hotspots of 247 cancer related genes were sequenced by next-generation sequencing. Mutations and their correlation with clinic-pathological factors were analyzed. The correlation between mutations and clinic-pathological factors was evaluated by χ² test or Fisher′s exact test. Results: Seventy-five patients were enrolled in this study. All patients were female and aged from 31 to 88 years with median age of 58 years. All patients′ clinic-pathological records were complete. Sixty-four mutations in 18 genes (ALK, BCR, ERBB2, ROS1, PDGFRA, EGFR, FGFR2, CYP1B1, CALR, CASP7, BRAF, FGFR1, FGFR3, MET, NRAS, PTEN, KIT, SOD2) were detected in 47 (62.7%) among all 75 patients.Exons were captured in 10 genes, and mutations in 2 of 3 genes analyzed were clustered. Gene mutations were not correlated with menopausal status, histological type, primary tumor (T), regional lymph nodes (N), TNM stage, histological grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, Ki-67 and molecular subtype (all P>0.05). Conclusion Circulating tumor DNA sequencing by next-generation sequencing was useful for detecting breast cancer-related mutations.