Endogenous Cushing's syndrome (CS) is rare, with an incidence of 0.7-2.4 per million population per year according to population-based studies. However, evaluation of patients presenting disorders potentially related to cortisol excess, and therefore with a 'high risk of clinical suspicion' profile, could bring out several unrecognized cases. CS represents one of the most challenging endocrine diseases, with clinical features overlapping with those of common conditions affecting general population, invariably resulting in potential mis- or delayed diagnosis with negative consequences in terms of morbidity and mortality. CS is remarkably prevalent among young females, variably presenting with menstrual irregularities and/or signs and symptoms of hyperandrogenism. Herein we briefly reviewed literature on prevalence and clinical impact of menses abnormalities, acne and hirsutism -also coexisting in the context of a polycystic ovary syndrome- in CS, aiming at clarifying if, when and how to screen for hypercortisolism young women with these disorders.