Fibromyalgia syndrome (FM) is an enigma. During the past three decades, with the gradual acceptance of the validity of FM, it is variously under-, over and misdiagnosed. Evidence-based interdisciplinary guidelines have suggested a comprehensive clinical assessment to avoid this diagnostic conundrum. Every patient with chronic pain should be screened for chronic widespread pain (pain in four of five body regions) (CWP). Those with CWP should be screened for presence of additional major symptoms of FM: unrefreshed sleep and fatigue. A complete medical (including drug) history and complete physical examination is mandatory in the evaluation of a patient with CWP in order to consolidate the diagnosis of FM or identify features that may point to some other condition that may have a presentation similar to FM. Limited simple laboratory testing is recommended to screen for possible other diseases. The 2016 criteria may be used to further confirm the clinical diagnosis of FM. In consideration of the differential diagnosis of FM, attention should be paid to the presence of other chronic overlapping pain conditions and of mental disorders. FM as a stand alone diagnosis is however rare, as most patients with FM meet criteria for other chronic overlapping pain conditions or mental disorders. The severity of FM should be assessed in order to direct treatment approaches and help inform the likely outcome for an individual patient.