Tissue sections were analyzed firstly by MALDI MSI using a SYNAPT G2-Si mass spectrometer with a MALDI source operating with a solid-state diode-pumped ND:YAG laser using a repetition rate of 1 KHz. The MALDI first sample preparation used was with CHCA in MeCH/Water. Consecutive tissues were then analyzed by DESI MSI, using a modified Prosolia source, directly mounted onto the SYNAPT G2-Si. Normal breast tissue is mammary fat pad, with a high presence of triglycerides (TG). DESI control tissue datasets, the highest signals were generated by the triglyceride molecules directly from the tissue sections i.e. m/z 879.74 (TG(54:6))H+ or (TG(52:3))Na+ and 853.73 (TG(52:5))H+ or (TG(50:2))Na+. The molecular profiles for breast tumor samples change with an increased intensity for the detection of phosphatidylcholine (PC). This was not observed with MALDI. MALDI triglyceride molecules were observed in both normal or cancerous tissue under the sample preparation conditions used. The observed difference for MALDI between the tissue types were more subtle and related to phospholipids. For example m/z 808.58 (PC(36:2))Na+ was less abundant in the tumor whereas m/z 772.52 (PC(32:0))K+ was more intense in the tumor sample. The lack of TGs in the MALDI datasets, resulted in a second preparation using CHCA in MeOH/Water, clearly showing the presence of TGs in control tissue and tumor bearing tissue. A third MALDI sample preparation using DHB in MeOH/Water will be tested to evaluate the nature of the lipids class ionized and to further examine the complementary nature of MALDI and DESI MSI.