<p>In postmortem studies, we have identified morphologic changes centered in and around Purkinje cells (PCs) in essential tremor (ET); these are indicative of cerebellar degeneration. Recent analyses of 100 ET and 50 control cerebella demonstrated that using <i>a combination</i> of these cerebellar morphologic metrics, which individually measure degenerative changes, correctly predicted a diagnosis of ET or control with sensitivity and specificity ~ 95%. Among the small proportion of ET cases that were misclassified, we questioned whether there was no evidence of cerebellar degeneration, or whether the cerebellar degeneration in these cases was simply more subtle. In this study, we used the diagnostic formula previously developed by a supervised classification model to evaluate an expanded sample of 156 ET and 71 control cerebella based on 8 metrics of cerebellar pathology that fell within one of six broad categories of morphologic change. We identified 14 ET and 11 controls among whom either the pathological classification failed (7 ET, 6 controls) or in whom metric scores were close to the diagnostic cutoff (7 ET, 5 controls); these were designated as having “clinical-pathological discordance” (CPD). All 14 ET-CPD cases had elements of neurodegeneration, with the majority (11/14) showing degenerative changes in <i>≥</i> 2 metrics. Moreover, one metric, if used in isolation, correctly diagnosed 72% of these ET-CPD cases. These analyses demonstrated the presence of subtle degenerative changes in the cerebellar cortex even among ET cases who were not classified as ET using our diagnostic algorithm.</p>