Four different types of core-shell tecto-(dendrimer) were imaged by tapping-mode atomic force microscopy (AFM). The tecto-(dendrimer) molecules were based on PAMAM dendrimers, and included G4G3, G5G3, G6G4, and G7G5 (the first number represents the generation number (G) of the core, and the second number, the generation number of the dendrimers in the shell). The individual tecto-(dendrimer) molecules could be clearly observed in the AFM images, which showed that their dimensions increased as a function of the sum of core-shell tecto-(dendrimer) generation values, i.e., G4G3 < G5G3 < G6G4 < G7G5. The molecular volumes of the tecto-(dendrimer) molecules could be directly obtained from the AFM images, from which molecular weights could then be estimated. The estimated molecular weights were in reasonable agreement with the results from matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and polyacrylamide gel electrophoresis (PAGE). We believe this represents a significant advance in the application of AFM because it provides a new method to directly measure the molecular volume (molecular weight) of macromolecules.