It was with great interest that we read the recent review by Sibbitt et al on neuroimaging in neuropsychiatric systemic lupus erythematosus (NPSLE) (1), which underlined the unquestionable role played by anatomic and functional imaging—along with careful clinical evaluation—in the diagnosis of NPSLE. In light of our own experience, however, we believe the role of nuclear medicine techniques in NPSLE diagnosis requires further consideration. As has been widely demonstrated, both positron emission tomography (PET) and single-photon emission computed tomography (SPECT) reveal alterations in flow and metabolism in NPSLE patients who have negative findings on magnetic resonance imaging (MRI) (2–4). The possibility that these PET and SPECT results are false-positive findings has been ruled out both by the fact that there are correlations with the results of other functional studies (5) and by the evidence of an ability to predict the neuropsychiatric evolution (6). Both SPECT and PET are rapidly developing technologies that are in constant evolution; moreover, both are increasingly available for clinical use, which has, predictably, reduced operating costs (7). Nevertheless, it must be emphasized that SPECT and PET both study cerebral function, and not its anatomy. They must therefore be integrated with some other morphologic imaging technique, in particular MRI, since an alteration in function (i.e., blood flow, cerebral metabolism) can understandably presage, or be closely related to, anatomic damage. Therefore, it is our opinion that correct use of neuroimaging techniques in NPSLE must, first of all, call for morphologic imaging (preferably with MRI) to rule out or confirm anatomic damage. Then, if the morphologic imaging result is negative and the neuropsychiatric status is still in doubt, functional imaging should be applied. The choice of technique should also be based on evidence found in the literature, availability, and local experience.