Tapping mode (TM) atomic force microscopy (AFM) has been applied in a novel fashion to characterize and distinguish the (001) and (100) surfaces of individual aspirin crystals. The surface characterization was achieved by amplitude-phase, distance (a-p,d) measurements employing gold-coated AFM probes functionalized with self-assembled monolayers (SAM). Experiments using model probes coated with -CH3 and -COOH terminated SAMs have been performed on the two aspirin crystal planes (001) and (100). Results indicate that the hydrophobic -CH3 terminated AFM probes had a greater degree of interaction with the crystal plane (001), whereas the -COOH terminated AFM probes had a larger interaction with the crystal plane (100). Interpretation of these data, based upon the chemistries of the probes, correlates with current understanding of the crystal surface chemistry derived from X-ray diffraction data and dissolution rate studies.