Immunohistochemistry with antibodies targeting enzymes responsible for the final conversion steps of cortisol (CYP11B1) and aldosterone (CYP11B2) is gaining ground as an adjunct tool in the postoperative evaluation of adrenocortical nodules. The method allows the pathologist to visualize hormone production for each lesion, thereby permitting a more exact assessment regarding the distinction between adrenocortical adenomas and adrenocortical hyperplasia, with implications for patient follow-up. We describe how immunohistochemistry facilitated the histopathological diagnosis of twin adenoma (one cortisol- and one aldosterone-producing) from suspected hyperplasia in a patient with hypertension, mild autonomous cortisol secretion and concurrent adrenocorticotropic hormone-producing adrenomedullary hyperplasia. As the nodules were similar in size and displayed rather analogous histology, CYP11B1 and B2 immunohistochemistry was needed to exclude adrenocortical hyperplasia, allowing us to discharge the patient from further surveillance. We conclude that the application of functional immunohistochemistry has direct clinical consequences and advocates the prompt introduction of these markers in clinical routine.