A retrospective study reviewed autopsy data from 84 children with suspected cerebral malaria (CM) at the Queen Elizabeth Central Hospital in Blantyre, Malawi, from 1996–2010. Of the 65 children who met the WHO clinical criteria for CM, 18 (28%) had no evidence of brain parasite sequestration at autopsy and 17 had an alternative cause of death. Malarial retinopathy had a sensitivity of 89.4% (95% CI 77.6–95.6%) and a specificity of 73.0% (95% CI 57.2–84.8%) for predicting brain parasite sequestration. With detailed retinal assessment, these values improved to a sensitivity of 94.3% (95% CI 81.7–98.7%) and a specificity of 88.0% (95% CI 70.4–96.2%) by reclassifying patients with fewer than 5 retinopathic hemorrhages in one eye as negative. The study is limited by the retrospective nature and selection bias of autopsies. Malarial retinopathy is the most specific clinical test for CM in endemic areas and its integration into management in different settings is suggested.