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Case Presentation: A 63-year-old man presented with fever, thoracalgia, weight loss, diffuse lymphadenopathy, and a massive pleural effusion. Extensive laboratory and radiologic investigations for possible autoimmune, infectious, hematologic, and neoplastic conditions all resulted negative. A lymph node biopsy showed a granulomatous necrotizing lymphadenitis, suspicious for tuberculosis. Although mycobacterium tuberculosis (MT) was never isolated and tuberculin skin test resulted negative, diagnosis of extrapulmonary tuberculosis was made and anti-tubercular therapy was started. Despite the strict adherence to 5 months of treatment, he returned to the emergency ward complaining of fever, chest pain and pleural effusion; total-body CT and PET scans demonstrated a progression of new disseminated nodular consolidations., Diagnostic Work-Up: Microscopic and cultural search for MT and other micro-organisms resulted again negative on urine, stool, blood, pleural fluid, and spinal lesion biopsy. We therefore started considering alternative diagnosis for necrotizing granulomatosis, including multidrug-resistant tuberculosis, Wegener granulomatosis, Churg Strauss syndrome, necrobiotic nodules of rheumatoid arthritis, lymphomatoid granulomatosis and Necrotizing Sarcoid Granulomatosis (NSG). Having already rejected other autoimmune, hematological, and neoplastic disorders, NSG resulted the most consistent hypothesis. With an expert we thus re-examined histological specimens that were suggestive for an atypical presentation of sarcoidosis. Steroid therapy was initiated, achieving symptoms improvement., Discussion: Sarcoidosis is a rare condition that can be challenging to diagnose, due to its variability in clinical presentation, often mimicking alternative conditions like disseminated tuberculosis. A high degree of suspicion and an experienced lab in anatomical pathology are essential for final diagnosis., (© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)