Fibromyalgia (FM) is a common pain disorder characterized by dysregulation in the processing of pain. Although FM has similarities with other rheumatologic pain disorders, the search for objective markers has not been successful. In the current study we analyzed gene expression in the whole blood of 70 fibromyalgia patients and 70 healthy matched controls. Global molecular profiling revealed an upregulation of several inflammatory molecules in FM patients and downregulation of specific pathways related to hypersensitivity and allergy. There was a differential expression of genes in known pathways for pain processing, such as glutamine/glutamate signaling and axonal development. We also identified a panel of candidate gene expression-based classifiers that could establish an objective blood-based molecular diagnostic to objectively identify FM patients and guide design and testing of new therapies. Ten classifier probesets (CPA3, C11orf83, LOC100131943, RGS17, PARD3B, ANKRD20A9P, TTLL7, C8orf12, KAT2B and RIOK3) provided a diagnostic sensitivity of 95% and a specificity of 96%. Molecular scores developed from these classifiers were able to clearly distinguish FM patients from healthy controls. An understanding of molecular dysregulation in fibromyalgia is in its infancy; however the results described herein indicate blood global gene expression profiling provides many testable hypotheses that deserve further exploration.