We report on a novel technique to nucleate nanometer-sized droplets on a solid substrate and to image them with minimal perturbation by noncontact atomic force microscopy (NC-AFM). The drop size can be accurately controlled, thus permitting hysteresis measurements. We have studied the nanoscale wettability of several methyl-terminated substrates prepared by the self-assembly of organic molecules. These substrates are alkyltrichlorosilanes on silica, alkylthiols on gold, alkyl chains on hydrogen-terminated silicon, and crystalline hexatriacontane chains on silica. For each of these systems, we report a deviation of the wetting contact angle from the macroscopic value, and we discuss this effect in term of mesoscale surface heterogeneity and long-range solid-liquid interactions.