A 60-year-old Caucasian male with a long history of cigarette smoking was diagnosed with epidermal growth factor receptor-mutation negative lung adenocarcinoma. The single cerebral metastasis in the right frontal lobe was treated with stereotactic radiosurgery and systemic chemotherapies. Normalized subtraction (NS) method was used to evaluate the serial brain magnetic resonance (MR) and fludeoxyglucose-positron emission tomography (FDG-PET) findings retrospectively, and the potential benefit of concurrent NS of serial MR images (MRIs) and PET images was demonstrated. MIM 4.1 (MIM Software Inc., Cleveland, OH) was used to co-register MRI with PET data and to perform NS on the serial MRI and PET data. MIM 4.1 provides fully automated alignment of imaging data by maximization of mutual information. Cortical regions distant from the brain lesion were used to adjust for the intensity differences between scans, so the voxel differences in normal brain regions were near zero in the NS images. A difference of 15% or greater in voxel densities was used for both MRI and PET, above or below which a change in MR signal intensity and FDG avidity was considered significant. The use of NS, in this case, allowed for an enhanced correlation of morphologic and functional information, which may have added value in the early treatment monitoring of brain tumors and help distinguish recurrent tumor from postradiation changes.