The aim of this study was to test by means of a voxel-based approach the hypothesis that there is a different spatial distribution of brain metastases (BM) and white matter hyperintensities (WMH) and that the presence of WMH affects the location of BM in lung and non-lung cancer patients. Two-hundred consecutive cancer patients at first diagnosis of BM were included. Images were acquired using a 1.5 Tesla MRI system (Magnetom Avanto B13, Siemens, Erlangen, Germany). Axial FLAIR T2 weighted images and gadolinium-enhanced T1 weighted images were post-processed for segmentation, co-registration and analysis. Binary lesion masks were created for WMH and BM, using Volumes of Interest. Lesion probability maps were generated and the voxel-based lesion-symptom mapping approach was used to model each voxel and to calculate a non parametric statistics (Brunner-Munzel test) describing the differences between the groups. In the lung cancer group we found higher frequency of BM in WMH- than in WMH+ patients in the occipital lobe and the cerebellum. In contrast, BM were more frequent in the right frontal lobe in WMH+ than in WMH- patients. We suggest that there exists an inverse brain spatial distribution between WMH and BM. In lung cancer patients, the presence of WMH seems to shift the distribution of BM toward locations different than what it is expected based on primary tumor.