The role of prolonged febrile seizures in the genesis of hippocampal sclerosis is controversial; statistical analysis and data from epilepsy surgery suggest a causal relationship. A three-year-old boy had an initial febrile seizure with a transient postictal flaccid hemiparesis. Magnetic resonance imaging (MRI) showed no abnormality of the hippocampal areas of both sides. At the age of four a prolonged febrile seizure occurred. An MRI was done immediately and gave abnormal results in the right hippocampal area where T2-weighted and dark fluid sequences showed increased signal intensity; in diffusion-weighted sequences this region appeared hyperintense, which is in agreement with acute neuronal damage. Six weeks later the right hippocampal region still gave hyperintense signals in MRI (T2-weighted), while the diffusion coefficient was unremarkable. A final MRI scan was done 16 months following the second febrile seizure where the right hippocampal region still gave hyperintense signals and was reduced in size as is typical for hippocampal sclerosis. This case illustrates the development of a hippocampal lesion following a prolonged focal febrile seizure without any preexisting hippocampal lesion or positive family history. This suggests that prolonged febrile seizures alone can be a causative factor of hippocampal sclerosis.