Selective symmetrical encephalomalacia (SSE) is a rare neurological disorder characterized by bilateral and symmetrical areas of malacia within specific regions of the central nervous system and has been reported in humans and several animal species. This report describes a case of SSE in a six-month-old Maine Coon crossbred kitten from Italy that presented with central vestibular dysfunction, rapidly progressive neurological deterioration, proprioceptive deficits, respiratory impairment, seizures, and abnormal vocalization. Clinical evaluation, hematological and biochemical analyses, and ancillary diagnostic testing were performed to investigate the underlying cause and evaluate differential diagnoses. Despite supportive care, the animal died naturally a few days after the onset of clinical signs. A complete postmortem examination, including histopathological evaluation of the central nervous system, was subsequently performed. Neuropathological analysis revealed multifocal, bilateral, and symmetrical malacic and spongiform lesions affecting multiple brain regions, compatible with an SSE pattern. Comparison with previously reported cases in humans and dogs showed marked similarities in lesion distribution and morphology. This case expands the limited knowledge of SSE-like neuropathological lesions in cats and highlights the value of neuropathological examination in the diagnosis of rare neurological disorders presenting with rapidly progressive clinical signs.