The microstructure of a body-centered cubic 20W-20Mo-20Cr-20Ti-20Al alloy in the as-cast condition as well as its microstructural evolution during heat treatment was investigated. Different characterization techniques, such as focused ion beam-scanning electron microscope, X-ray diffraction, and transmission electron microscope, were applied. Experimental observations were supported by thermodynamic calculations. The alloy exhibits a pronounced dendritic microstructure in the as-cast condition with the respective dendritic and interdendritic regions showing significant fluctuations of the element concentrations. Using thermodynamic calculations, it was possible to rationalize the measured element distribution in the dendritic and the interdendritic regions. Observations of the microstructure evolution reveal that during heat treatment, substantial homogenization takes place leading to the formation of a single-phase microstructure. Driving forces for the microstructural evolution were discussed from a thermodynamic point of view. © 2015 The Minerals, Metals & Materials Society and ASM International