Advancing insights into fibromyalgia: an updated review of diagnosis and differential diagnosis

INTRODUCTION: Despite advances in understanding nociplastic pain and central sensitization, fibromyalgia remains a challenging clinical diagnosis due to the absence of specific biomarkers, extensive symptom overlap with other conditions, and persistent misconceptions about its pathophysiology. AREAS COVERED: This narrative review covers the evolution of the diagnostic criteria, the clinical presentation, the red flags suggesting alternative diagnoses, and a practical diagnostic approach toward fibromyalgia. Attention is given to its differential diagnosis with rheumatological, neurological, endocrine, sleep, and psychiatric conditions as well as other overlap syndromes, along with emerging tools including quantitative sensory testing, small fiber pathology, neuroimaging, and digital phenotyping. Evidence was identified through a search of PubMed and Web of Science (April to May 2026) for 'fibromyalgia' combined with key terms, supplemented by hand-searching reference lists and recent systematic reviews. EXPERT OPINION: Fibromyalgia should be approached not as a diagnosis of exclusion but as a recognizable nociplastic pain syndrome requiring mechanism-informed evaluation. In practice, this means applying the American College of Rheumatology 2010/2016 criteria positively, limiting work-up to a five-test panel (complete blood count, erythrocyte sedimentation rate, C-reactive protein, thyroid-stimulating hormone, and creatine kinase if weakness is present) unless red flags dictate otherwise, and only when diagnostic uncertainty, red flags, or overlapping inflammatory disease persist.