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 mu m 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.