A retrospective study of brain lesions in goats was conducted to identify the range of lesions and diseases recognized and to make recommendations regarding the best tissues to examine and tests to conduct in order to maximize the likelihood of making a definitive diagnosis in goats that may have had clinical signs referable to the brain. One hundred thirty-nine goats with a brain lesion were identified. The most common lesion, in 52.5% of the goats, was suppurative inflammation. Approximately two-thirds of these goats had encephalitic listeriosis. Other goats were found to have suppurative inflammation in association with septicemia, pituitary abscesses, dehorning injury, and otitis. Thirty goats (21.6%) were diagnosed with polioencephalomalacia. Twenty-one goats (15.1%) were diagnosed with nonsuppurative inflammation. In more than half of these goats, no definitive diagnosis was made, while 8 were infected with Caprine arthritis encephalitis virus and 1 with Rabies virus. However, few goats were tested for rabies. Based on these findings, it is recommended that, in addition to appropriate handling of the brain, the head should be examined with attention paid to the sella turcica and the temporal bones for evidence of a pituitary abscess and otitis, respectively. Histologic examination should include multiple areas of the brain, including the brainstem, for lesions of encephalic listeriosis; the cerebral cortex, for lesions of polioencephalomalacia; and the hippocampus, for Negri bodies associated with Rabies virus infection. Consideration should be given to collecting samples of other tissues including, but not limited to, the spinal cord and liver for ancillary testing if warranted.