A void region exists in some biological tissues, and previous studies have shown that inaccurate images would be obtained if it were not processed. A hybrid radiosity-diffusion method (HRDM) that couples the radiosity theory and the diffusion equation has been proposed to deal with the void problem and has been well demonstrated in two-dimensional and three-dimensional (3D) simple models. However, the extent of the impact of the void region on the accuracy of modeling light propagation has not been investigated. In this paper, we first implemented and verified the HRDM in 3D models, including both the regular geometries and a digital mouse model, and then investigated the influences of the void region on modeling light propagation in a heterogeneous medium. Our investigation results show that the influence of the region can be neglected when the size of the void is less than a certain range, and other cases must be taken into account.