Prostate adenocarcinoma is a very rare cause of ectopic adrenocorticotropic hormone (ACTH) syndrome. We report the case of a 70-year-old man who presented with clinical and biochemical features of ACTH-dependent Cushing syndrome secondary to prostate carcinoma. On admission, his blood pressure was 170/100 mm Hg. Physical examination revealed signs of excessive production of cortisol. Laboratory values were consistent with hypokalemia and metabolic alkalosis. Elevated serum cortisol, ACTH, and urine free cortisol levels were found. Cortisol was not suppressed with an overnight 1-mg oral dexamethasone suppression test (DST), 2-day low-dose DST, or overnight 8.0-mg high-dose DST. Chest computed tomography showed multiple parenchymal nodules in the right lung, consistent with metastatic disease. Whole-body bone scintigraphy revealed numerous foci of increased radiotracer uptake in the femur and axial skeleton, consistent with metastatic disease. Bone survey (radiography) showed generalized osteolytic metastases. Histologic analysis of a prostatic biopsy showed prostate adenocarcinoma. Immunostaining of the prostate adenocarcinoma for ACTH was positive. The severe metabolic alkalosis due to glucocorticoid-induced mineralocorticoid excess was treated with potassium supplements and spironolactone. This case is a remarkable example of the complex metabolic endocrine manifestations that can accompany prostate adenocarcinoma.