Abstract An ultrathin bilayer Pb–Al film was made by cold rolling and ion beam thinning techniques. Morphological instability of the Pb layer under electron beam irradiation was investigated by means of in situ transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HRTEM). Morphological instability of the Pb layer was characterized by spheroidization of Pb film and coalescence of Pb particles. Under electron beam irradiation, the ultrathin Pb layer with an incoherent Pb–Al interface was unstable and sphericized into Pb particles with an initial size about 3 nm. The Pb particles were mobile on the Al substrate and the coalescence of Pb particles took place. The Pb particles grew up only in the way of coalescence and the mobility of the particles decreased with the particle size increasing. The growth rates of Pb particles in different stages of coalescence were measured, respectively. The mechanism of spheroidization and coalescence was discussed. Driving forces for the spheroidization and the coalescence were attributed to minimizing the total energy. The intensive motion of the surface atoms for the Pb films and particles under irradiation activated the morphological instability of the system.