One of the main problems regarding the follow-up of patients with brain tumours treated with radiotherapy is the distinction between radiation necrosis and tumour relapse. In many cases computed tomography (CT) scan is unable to distinguish between the two. We assessed the usefulness of brain single-photon emission tomography (SPET) with technetium-99m-sestamibi in cases where CT scan was not conclusive. The absence of tracer uptake in normal brain, the sharp uptake in neoplastic tissue, and the favourable physical properties of technetium make the scintigraphic method particularly accurate. We therefore propose the association of CT scan with 99mTc-sestamibi brain SPET in the follow-up of patients in whom a distinction between radiation necrosis and active disease is needed for an adequate therapeutic decision.