A 14-year-old female post-transplant patient with a history of post-transplant lymphoproliferative disease/lymphoma presented with fever and lethargy. Computed tomography of the brain demonstrated a hypodense lesion with surrounding edema in the right periventricular region not seen on a routine study performed two weeks earlier. On magnetic resonance imaging (MRI) this lesion was mainly iso-intense to gray matter on T2-weighted (T2W) images and demonstrated peripheral contrast enhancement. Diffusion restriction was seen within most of the lesion including, but not limited to, its periphery. Lesion location and MRI characteristics, particularly on T2W and diffusion sequences, were suggestive of lymphoma. The patient's history of post-transplant lymphoproliferative disorder also supported this diagnosis. However, in view of the patient's immunocompromised state, rapid onset of symptoms, and recent normal CT scan of the brain, infection was also entertained. Biopsy revealed short branching hyphae consistent with aspergillosis. This case is interesting as the MRI restriction pattern and the patient's history were more suggestive of lymphoma, but in reality the lesion represented an evolving aspergillosis abscess. Biopsy was necessary to further proceed with appropriate medical management, which is significantly different for the two entities.