The aim of this study was to determine whether nested generic box models can be used to predict spatial variance. An inter-comparison study was performed for the nested box model SimpleBox, and the spatially resolved model LOTOS-EUROS, using PCB-153 emissions in Europe as an example. We compared the two models concerning (1) average environmental concentrations, (2) spatial concentration variances, (3) spatial concentration patterns (maps), and (4) agreement with measured concentrations for the air and soil compartments. In SimpleBox, the spatial concentration variances and patterns were calculated subsequently for each separate grid cell surrounded by a regional and a continental shell with homogeneous, averaged circumstances. Average European PCB-153 concentrations calculated by LOTOS-EUROS and SimpleBox for the period 1981-2000 agree well for the air and soil compartments. Moreover, the predicted concentrations of both models are in line with the measured PCB-153 concentrations in Europe during that period. For PCB-153, the prediction of spatial concentration variances with the nested multimedia fate model SimpleBox performs adequately in most cases, except for the lower concentration boundary in the air compartment. It is concluded that SimpleBox can be used to predict the spatial maximum and average concentrations of PCB-153 in the air and soil compartments. The proposed method has to be tested systematically for different types of compounds, emission scenarios, environmental compartments and spatial scales in order to allow conclusions about the general applicability of the method.