Patients with fibromyalgia (FM) may present manifestations such as arthralgias, subjective joint swelling, fatigue, and ANA positivity, which are suggestive of a connective tissue disorder (CTD). The purpose of this study was to determine whether patients with FM and positive antinuclear antibodies (ANA), have features distinct from those who are ANA negative. Sixty-nine patients with FM who were participating in a longitudinal study were evaluated for the presence or absence of ANA (by indirect immunofluorescence using Hep-2 cells as substrates) and for manifestations suggestive of a systemic CTD. Eighteen of the 69 patients with FM (26.1%) were ANA positive and at a titer ≤1:80 (~78%, speckled pattern); their clinical manifestations were comparable to those of the 51 ANA-negative patients. Thus, ANA was not associated with any difference in the pattern of FM. Also, ANA-positive patients with FM are no more likely to exhibit symptoms suggestive of systemic CTDs than ANA-negative patients. Caution should be exercised in the management of these patients to avoid the unnecessary use of therapeutic agents not otherwise indicated and potentially toxic.