Multiple ring-enhancing lesions of the brain are one of the most commonly encountered abnormalities on neuroimaging. These can be caused by a variety of infectious, neoplastic, inflammatory or vascular diseases. Distinguishing non-neoplastic causes from neoplastic lesions is extremely important because a misdiagnosis can lead to unwarranted neurosurgery and exposure to toxic chemotherapy or potentially harmful brain irradiation. Diligent clinical evaluation and a battery of tests are required for making a definitive diagnosis. Newer advanced diagnostic techniques, such as diffusion-weighted magnetic resonance imaging (MRI), perfusion-weighted MRI, magnetic resonance spectroscopy, single-photon emission tomography and positron emission tomography may help in establishing the etiology. However, early brain biopsy is often needed because several of these diseases are potentially life-threatening.