We hereby describe a patient in whom chronic rifampicin treatment led to a misdiagnosis of Cushing's syndrome. He had long-standing insulin-dependent diabetes mellitus and active tuberculosis resistant to conventional treatment. The course was complicated by muscle weakness, lower limb atrophy, unstable glycemic control and hypokalemia. Ectopic Cushing's syndrome was suspected on the basis of high urinary free cortisol excretion (UFC) with a blunted circadian profile of serum cortisol and measurable plasma ACTH concentrations. Dynamic endocrine tests and imaging studies were compatible with occult ectopic ACTH syndrome. After substitution of rifampicin UFC excretion returned to normal within two weeks, as well as the 24-h cortisol profile and dynamic tests. The present case provides a practical example of the possibility to incorrectly suspecting Cushing's syndrome in patients treated with rifampicin, as previously envisaged by pharmacological studies.