Primary aldosteronism (PA), including aldosterone and cortisol producing adenoma (A/CPA), is the most common trigger of secondary hypertension. The prevalence of A/CPA may be higher than what we could recognize previously with similar studies, but only a few relevant immunohistochemical reports have confirmed this information. Collecting more clinical features and immunohistochemistry data may help us to understand A/CPA, which is very important for avoiding misdiagnosis and improving outcomes in patients with A/CPA.Both individuals included in this study had hypertension for >10 years. Computed tomography scans revealed the presence of adrenal nodules 1 year ago in patient A and 10 months ago in patient B (based on the date of the final version of this report). The relevant clinical features support PA accompanied by subclinical Cushing syndrome.Aldosterone and cortisol producing adenoma.The adrenal adenoma on the affected side was removed and pathological examination and immunohistochemistry were performed. Both the patients received short-term hydrocortisone treatment.The blood pressure of both patients improved after surgery. Cytochrome P450 (CYP)11B1, CYP11B2, parathyroid hormone receptor 1 (PTH1R), calcium-sensing receptor (CaSR), and vitamin D3 receptor (VD3R) were all positively expressed, but the histopathological features of the expression region differed.The occurrence of A/CPA may be related to calcium metabolism disorders. For A/CPA, the diversity in immunohistochemistry suggests many uncertainties regarding the pathogenesis of the disease. A/CPA should be considered in new clinical and pathological classifications of PA to gain more attention from the medical community.Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.