BackgroundSpontaneous hyperadrenocorticism (HAC) is rare in cats. Clinical findings, diagnostic test results, and response to various treatment options must be better characterized.ObjectivesTo report the clinical presentation, clinicopathologic findings, diagnostic imaging results, and response to treatment of cats with HAC.AnimalsCats with spontaneous HAC.MethodsRetrospective descriptive case series.ResultsThirty cats (15 neutered males, 15 spayed females; age, 4.0–17.6 years [median, 13.0 years]) were identified from 10 veterinary referral institutions. The most common reason for referral was unregulated diabetes mellitus; dermatologic abnormalities were the most frequent physical examination finding. Low‐dose dexamethasone suppression test results were consistent with HAC in 27 of 28 cats (96%), whereas ACTH stimulation testing was suggestive of HAC in only 9 of 16 cats (56%). Ultrasonographic appearance of the adrenal glands was consistent with the final clinical diagnosis of PDH or ADH in 28 of 30 cats (93%). Of the 17 cats available for follow‐up at least 1 month beyond initial diagnosis of HAC, improved quality of life was reported most commonly in cats with PDH treated with trilostane.Conclusions and Clinical ImportanceDermatologic abnormalities or unregulated diabetes mellitus are the most likely reasons for initial referral of cats with HAC. The dexamethasone suppression test is recommended over ACTH stimulation for initial screening of cats with suspected HAC. Diagnostic imaging of the adrenal glands may allow rapid and accurate differentiation of PDH from ADH in cats with confirmed disease, but additional prospective studies are needed.