The stability of Ni, Cu, Mo and Au transmission electron microscope (TEM) grids coated with ultra-thin amorphous carbon (α -C) or silicon monoxide film is examined by in-situ heating up to a temperature in the range 500–850 °C in a transmission electron microscope. It is demonstrated that some grids can generate nano-particles either due to the surface diffusion of metal atoms on amorphous film or due to the metal evaporation/redeposition. The emergence of nano-particles can complicate experimental observations, particularly in in-situ heating studies of dynamic behaviours of nano-materials in TEM. The most widely used Cu grid covered with amorphous carbon is unstable, and numerous Cu nano-particles start to form once the heating temperature reaches 600 °C. In the case of Ni grid covered with α -C film, a large number of Ni nano-crystals occur immediately when the temperature approaches 600 °C, accompanied by the graphitization of amorphous carbon. In contrast, both Mo and Au grids covered with α -C film exhibit good stability at elevated temperature, for instance, up to 680 and 850 °C for Mo and Au, respectively, and any other metal nano-particles are detected. Cu grid covered Si monoxide thin film is stable up to 550 °C, but Si nano-crystals appear under intensive electron beam. The generated nano-particles are well characterized by spectroscopic techniques (EDXS/EELS) and high-resolution TEM. The mechanism of nano-particle formation is addressed based on the interactions between the metal grid and the amorphous carbon film and on the sublimation of metal.