A 36-yr-old man with AIDS exhibited intense 201Tl uptake (lesion-to-brain uptake ratio 5.38) in a brain lesion previously detected by MRI and CT. The lesion was biopsied and found to contain cells with viral inclusions diagnostic of cytomegalovirus infection, not tumor as the thallium SPECT results suggested. Thallium-201 SPECT may be less specific than previously reported for differentiating neoplastic disease from opportunistic infections in AIDS patients.