AbstractFine-needle aspiration cytology (FNAC) is commonly used to obtain a pre-surgical pathological diagnosis in many organs, but its cost-effectiveness in lymphadenopathy has not been studied yet. We calculated the cost and diagnostic accuracy of a diagnostic algorithm that uses FNAC as a first-line procedure and compared it to a purely surgical approach in 545 consecutive lymphadenopathies. In 74% of the cases, FNAC alone can obtain a sufficiently detailed diagnosis, avoiding the surgical biopsy. In doing so, the average cost of diagnosis is cut to less than one-third, the patient avoids an invasive procedure and the diagnosis is reached earlier. In conclusion, the systematic use of lymph node-FNAC in the initial assessment of lymphadenopathy is clinically and economically advantageous as it avoids surgical biopsies in cases where cytology can suffice.