Hemoglobin electrophoresis is the method most commonly used to diagnose sickle cell trait (SCT) at autopsy. However, in some cases, this accepted technique is unable to be used due to either insufficient sampling, sample degradation, or lack of forethought; histology samples and/or gross tissue are not subject to these sampling errors and are routinely taken during autopsies. In this study, we attempted to determine whether one can reliably diagnose SCT using histology only. Histology sections of commonly sampled tissues (primarily heart, lung, and liver) from 9 decedents with SCT, 3 decedents with hemoglobin SC disease, and 18 control cases were examined in a blinded fashion as single slides and then as slide sets. When evaluating slide sets, the reviewers were able to identify the cases with SCT (sensitivity = 95%, specificity = 100%). Such samples could be used to diagnose SCT even decades after the original death certification and long after samples necessary for other techniques have degraded or been discarded.