Abstract This paper is concerned with the development of entropy-based registration criteria for automated 3D multi-modality medical image alignment. In this application where misalignment can be large with respect to the imaged field of view, invariance to overlap statistics is an important consideration. Current entropy measures are reviewed and a normalised measure is proposed which is simply the ratio of the sum of the marginal entropies and the joint entropy. The effect of changing overlap on current entropy measures and this normalised measure are compared using a simple image model and experiments on clinical image data. Results indicate that the normalised entropy measure provides significantly improved behaviour over a range of imaged fields of view.