Mast cells (MCs) accumulate in the stroma surrounding tumors and take part in the inflammatory reaction occurring at the margin of the neoplasia. Moreover, MC secretes angiogenic cytokines and matrix metalloproteinases. The aim of this study was to investigate the pattern of distribution of MCs in biopsy samples obtained from four different human tumors, utilizing an image analysis system and a mathematical model to make a quantitative approach to characterizing their spatial distribution. Results showed a similar spatial arrangement of MCs in all the neoplastic tissues examined, despite histological and/or pathologic differences. In all these tissues MCs demonstrated a virtually random spatial distribution, albeit with varying densities. These results suggest that MC-MC interactions could play a minor role in the formation of the MC pattern in neoplastic tissues. The random distribution of the cells in the tissues could be accounted for by a random walk-migration under the influence of cell-matrix interactions or chemotactic fields potentially generated by tumor or endothelial cells.