The Endocrine Society has developed clinical practice guidelines for the diagnosis of Cushing's syndrome. The guidelines recommend testing for Cushing's syndrome in patients with multiple and progressive features, particularly those with a high discriminatory value, and patients with adrenal incidentaloma. Initial testing should include one of the following: urine free cortisol (UFC), late-night salivary cortisol, 1-mg overnight dexamethasone suppression test (DST), or longer low-dose DST (2 mg/d for 48 h). Patients with abnormal results should see an endocrinologist for further evaluation, while those with concordant normal results should not undergo further evaluation. Discordant results, normal responses suspected of cyclic hypercortisolism, or additional features over time warrant further testing. The guidelines also provide recommendations for special populations, such as pregnant women, patients with epilepsy, renal failure, cyclic Cushing's syndrome, and adrenal incidentaloma. The development of these guidelines was guided by systematic reviews of evidence and discussions, and they were reviewed and approved by various committees of the Endocrine Society.The Endocrine Society has developed clinical practice guidelines for the diagnosis of Cushing's syndrome. The guidelines recommend testing for Cushing's syndrome in patients with multiple and progressive features, particularly those with a high discriminatory value, and patients with adrenal incidentaloma. Initial testing should include one of the following: urine free cortisol (UFC), late-night salivary cortisol, 1-mg overnight dexamethasone suppression test (DST), or longer low-dose DST (2 mg/d for 48 h). Patients with abnormal results should see an endocrinologist for further evaluation, while those with concordant normal results should not undergo further evaluation. Discordant results, normal responses suspected of cyclic hypercortisolism, or additional features over time warrant further testing. The guidelines also provide recommendations for special populations, such as pregnant women, patients with epilepsy, renal failure, cyclic Cushing's syndrome, and adrenal incidentaloma. The development of these guidelines was guided by systematic reviews of evidence and discussions, and they were reviewed and approved by various committees of the Endocrine Society.