Abstract In this paper we present our latest developments in high precision positioning and handling systems operating inside Scanning Electron Microscopes (SEM). This work is motivated by the growing need of new instruments for the in-situ analysis of materials. In the medium terms, these instruments will permit more laboratories to accomplish complex and repetitive tests on several samples and with various tools, without the need to open the SME chamber, increasing thus productivity and improving the reliability of the analysis. The concept of a complete manipulator system, working inside a SEM chamber (Lab-In-SEM: LIS) is proposed. Then the performances of a miniature-indenter -scratch(Miniatureindenter-scratch for SEM chamber: MISS) are described and compared with the commercial instrument MTS-XP. Examples of nano-indentation and scratch operations will be described. Then we present a five degrees-of-freedom manipulator (Ztilt-5). The Ztilt-5 has a resolution of 100nm, a workspace of several cubic centimeters and can lift weight up to 300 g. Its geometrical model has been implemented on a PC-based controller allowing telemanipulation, and joint or task spaces control. The Ztilt-5 is powered with a new type of piezo-actuators.