AbstractHippocampal sclerosis (HS) refers to loss of hippocampal neurons and astrogliosis. In temporal lobe epilepsy (TLE),HSis a key factor for pharmacoresistance, even though the mechanisms are not quite understood. While experimentalTLEmodels are available, there is lack of models reflecting the naturalHSdevelopment. Among domestic animals, cats may present withTLE‐like seizures in natural and experimental settings. With this study on the prevalence, segmental pattern and clinicopathological correlates of felineHS, we evaluated the translational value for human research. Evaluation schemes for human brains were applied to epileptic cats. The loss of neurons was morphometrically assessed and the degree of gliosis was recorded. Hippocampal changes resembling humanHSwere seen in about one third of epileptic cats. Most of these were associated with infiltrative diseases such as limbic encephalitis. Irrespective of the etiology and semiology of seizures, total hippocampal sclerosis was the most prevalent form seen in epileptic animals. OtherHStypes also occur at varying frequencies. Segmental differences to humanHScan be explained by species‐specific synaptic connectivities and a different spectrum of etiologies. All these variables require consideration when translating results from feline studies regarding seizure‐associated changes of the temporal lobe and especiallyHS.