To find new biomarkers for early diagnosis of breast cancer. 847 lipid species were identified from 78 plasma samples (37 breast cancer samples and 41 healthy controls) by ultra HPLC coupled with quadrupole time-of-flight tandem mass spectrometry. These include 321 glycerophospholipids (GPs), 265 glycerolipids (GLs), 91 sphingolipids (SPs), 77 fatty acyls (FAs), 68 sterol lipids (STs), 18 prenol lipids (PRs), 6 polyketides (PKs), and 1 saccharolipid (SL). Separation was observed from an orthogonal signal correction Partial Least Square Discrimination Analysis model. Based on this analysis, six differentiating lipids were identified: PC (20:2/20:5), PC (22:0/24:1), TG (12:0/14:1), and DG (18:1/18:2) had high levels, whereas PE (15:0/19:1) and N-palmitoyl proline had low levels in the breast cancer samples compared with the healthy controls. Furthermore, significant differences in metabolites were found among some clinical characteristics. Our results reveal that six specific lipids could serve as potential biomarkers for early diagnosis of breast cancer.