Desorption electrospray ionization mass spectrometric imaging (DESI-MSI) has been shown to be particularly powerful for identifying lipids and metabolites directly from tissue sections and providing a chemical map of their distribution. We applied DESI-MSI to investigate changes in lipid profiles that occur in animal and human lymphomas associated with the overexpression of the v-myc avian myelocytomatosis viral oncogene homolog (MYC). Using statistical analysis, we found 86 lipids that were either increased or decreased in MYC-induced transgenic mouse models of lymphoma. Most of the increased lipids were glycerophosphoglycerols and cardiolipins with a higher content of monounsaturated fatty acids when compared with control tissue. The lipid profiles of MYC associated human lymphomas with overexpression of MYC resemble closely those observed in MYC-induced transgenic mouse models.