Case summary An 18-month-old castrated male domestic shorthair cat was presented with a 2-month history of collapse and severe weakness, particularly affecting the pelvic limbs. A biceps femoris muscle biopsy revealed excessive variability in myofibre size, mild necrosis, minimal centronucleation and scattered 10 μm intracytoplasmic oval inclusions. The inclusions appeared amphophilic with haematoxylin and eosin, blue with Gomori trichrome and unstained with nicotinamide adenine dinucleotide dehydrogenase tetrazolium reductase staining. ATPase staining revealed a normal mosaic pattern and atrophy of both type 1 and 2 myofibres. The pathological diagnosis was a myopathy with inclusions. In contrast to previous feline myofibre inclusions previously reported in the literature, inclusions were not identified after immunohistochemistry using anti-desmin, tubulin, spectrin, laminin, LAMP and LC3 antibodies. After supportive care and corticosteroid treatment, clinical improvement was noted and the cat was discharged 10 days after initial presentation. Clinical and neurological re-examinations were performed at 1, 3, 6 and 9 months after discharge. Owner contact at both 10 and 30 months post-discharge confirmed that persistent muscular weakness was present. Relevance and novel information This case report describes a novel and slowly progressive feline myopathy associated with oval amphophilic inclusions unreactive to immunostaining, which have not been previously reported in feline myopathies.