We present a patient with new onset temporal lobe epilepsy and cognitive decline in his sixth decade with unilateral hippocampal atrophy on structural brain imaging, compatible with mesial temporal sclerosis. This unusual clinical scenario presented a challenging differential diagnosis since it may overlap with primary cognitive disorders, including early-onset Alzheimer's disease and some forms of frontotemporal dementia, and the recently elucidated syndrome of non-paraneoplastic limbic encephalitis associated with voltage-gated potassium channel antibodies.