A cassette changing device for a microtome has a housing (1) having a loading opening (3), a transfer opening (5) and an unloading opening (7). The openings are arranged with respect to each other linearly in the housing. A slide (10) is disposed in the housing linearly movably between a first position and a second position and has a first loading compartment (12) and a second loading compartment(13). The first and second compartments are aligned with respect to each other so that, at each terminal position of the slide, the first compartment and the second compartment are respectively aligned with a pair of openings. In a method using the cassette changing device to change a cassette, at a first terminal position of the slide, loading a cassette to the first loading compartment through the loading opening; moving the slide to a second terminal position, transferring the cassette from the first loading compartment through the transfer opening, moving the slide to the first terminal position, and loading the first loading compartment again, after transferring the cassette, loading the transferred cassette in the second loading compartment; moving the slide to the second terminal position, unloading the loaded cassette from the second loading compartment through the unloading opening, transferring the cassette from the first loading compartment for treatment; repeating the two steps above.