Statistical modeling of mass spectrometry imaging (MSI) data is a crucial component for the understanding of the molecular characteristics of cancerous tissues. Quantification of the abundances of metabolites or batch effect between multiple spectral acquisitions represents only a few of the challenges associated with this type of data analysis. Here we introduce a method based on ion co-localization features that allows the classification of whole tissue specimens using MSI data, which overcomes the possible batch effect issues and generates data-driven hypotheses on the underlying mechanisms associated with the different classes of analyzed samples.