BACKGROUND:Fine needle aspiration (FNA) cytology has been widely used for pathologic assessment of breast lesions. However, the examination suffers a risk of false-negative results owing to insufficient sample volumes, inaccurate sampling positions, nondefinitive cytologic features, or suboptimal cell preservation. One approach to improve its accuracy is using modern mass spectrometry to detect disease biomarkers, of which the tissue samples are collected through FNA. METHODS:The biological compounds in the FNA tissue samples were extracted and characterized by matrix-assisted laser desorption ionization time-of-flight/mass spectrometry (MALDI-TOF/MS). The results were further analyzed by principal component analysis. Distribution of lipid biomarkers on tissues was explored by imaging mass spectrometry. RESULTS:Lipid profiles of the tissue samples collected by FNA were rapidly obtained through MALDI-TOF/MS analysis. Phosphatidylcholines and triacylglycerols were detected as the predominant compounds in cancerous and normal regions, respectively. The samples were clearly classified by principal component analysis, based on the differences in their lipid profiles. Different lipid patterns were clearly viewed through the molecular imaging of normal and tumorous regions of breast tissue samples. CONCLUSION:The FNA-MALDI-TOF/MS approach can provide complementary information for pathological examinations and improve the accuracy of breast cancer diagnoses. Owing to the ease of operation and automation, it is possible to efficiently screen the lipid biomarkers in a large number of tissue samples by means of MALDI-TOF/MS.