A system and method are disclosed which enable manipulation of a sample under study with a microscope. In one embodiment, a manipulation system is adaptable for interfacing with any of a plurality of different types of microscopes, such as a transmission electron microscope (TEM) and a scanning electron microscope (SEM), and further comprises at least one manipulation mechanism operable to manipulate a sample. In another embodiment, a manipulation system is capable of being detachably coupled to a microscope, such as a TEM, and comprises a plurality of manipulator mechanisms for manipulating a sample. In a preferred embodiment, the manipulation system comprises both an adjustable interface such that it is capable of selectively coupling with any of a plurality of different microscope interfaces and a plurality of manipulator mechanisms integrated therein that are controllably operable for manipulating a sample.