Cushing’s syndrome is an endocrine disorder broadly renowned as a diagnostic challenge. From the initial clinical presentation up to the identification of the underlying etiology, it is necessary to adhere to a logical and stratified plan of action, directed to the correlation of signs and symptoms to the physiopathology of the syndrome, in order to accurately establish a diagnosis and adequate treatment. From stages as early as the patient’s first clinical evaluation, the physician should be specially attentive of a constellation of clinical signs which strongly suggest the diagnosis of Cushing’s syndrome, such as the presence of a “moon face”, a “buffalo hump”, cutaneous atrophy, proximal muscle weakness and purplish cutaneous striae, among others. Based off these findings, laboratory analyses are necessary for the detection of hypercortisolism. According to these results, and if physiologic causes are ruled out, pathologic hypercortisolism is confirmed. Lastly, a complex array of diagnostic tests must be navigated to identify the primary origin of the disorder. Thus, the diagnosis of Cushing’s syndrome requires a logically structured algorithm of action, constructed off its pathophysiologic implications, in order to optimize time, resources and the interdisciplinary workgroup required for its consecution, and offer patients the possibility of a better quality of life. It is also important to highlight the need for a stratified approach in patients with metabolic disturbance given that medical professionals may simply treat the patient for obesity not recognizing the presence of the complicating condition Cushing’s syndrome.