Although the clinical and biochemical discrimination of true Cushing syndrome from the Cushing phenotype is sometime difficult, four diagnostic studies are currently used: late-night serum and salivary cortisol level, urine free cortisol level, low-dose dexamethasone suppression, and the dexamethasone-CRH test. Using these tests, 90% of patients with Cushing syndrome are diagnosed. Once the diagnosis of the Cushing syndrome is firmly established, the next step is differential diagnosis of the subtype. Furthermore, the differentiation of pituitary and ectopic ACTH-dependent Cushing syndrome should be carried out using measurement of ACTH. Finally, bilateral petrosal sinus sampling for ACTH with CRH administration might be a powerful tool for a diagnosis for ectopic ACTH syndrome. A variety of benign and malignant tumors of non-pituitary tissues have been associated with the ectopic ACTH syndrome. The tumors most commonly associated with ACTH syndrome arise from neuroendocrine tissues, however, the pathogenesis of the ectopic ACTH syndrome remains unknown.