Objective: To screen patients with fibromyalgia for bipolar disorder and to determine if there were any clinical clues, other than the Mood Disorders Questionnaire (MDQ), which might suggest a diagnosis of comorbid bipolar disorder. Methods: A total of 128 consecutive new fibromyalgia patients referred to a tertiary care center rheumatology practice were enrolled and assessed using a standard clinical protocol that included the completion of four screening questionnaires: (i) MDQ for bipolar disorder, (ii) Beck Depression Inventory (BDI) for depression, (iii) Epworth Sleepiness Scale (ESS) for daytime sleepiness, and (iv) Fibromyalgia Impact Questionnaire Disability Index (FIQ-DI) to assess for functional capacity. Results: A quarter of the fibromyalgia subjects, 25.19%, had a positive screen for bipolar disorder (MDQ >= 7); 78.12% were clinically depressed (BDI >= 10); and 52.13% reported daytime sleepiness (ESS >= 10). Fibromyalgia subjects who screened positive for bipolar disorder had more severe depression than those with a negative screen [median BDI: 26.0 (19.0, 32.0) versus 15.0 (9.0, 24.0), p < 0.001]. Conclusions: We report a high prevalence of positive testing for bipolar disorder in this fibromyalgia cohort. Clinical data and questionnaire instruments other than nonspecific high depression severity failed to identify these patients. Since the norepinephrine serotonin reuptake inhibitors duloxetine and milnacipran have been recently approved by the U.S. Food and Drug Administration for the treatment of fibromyalgia, and because patients with bipolar disorder may experience destabilization of mood when treated with such agents, patients with fibromyalgia should be systematically screened for bipolar disorder prior to treatment.