Fine-needle aspiration (FNA) of thyroid nodules has markedly reduced the role of thyroid scintigraphy. This is often limited to nondiagnostic or follicular (tumor) FNA classifications. In this study, we evaluated the efficacy and cost of such a strategy in a university center. From 1992-1998, 995 aspirations were done in 667 patients with palpable nodules. FNA was classified as malignant, suspicious, follicular, benign or inadequate. The Gold standard was surgery or extended follow-up, including physical examination, FNA, and/or ultrasound (US) with a time interval of half a year. Cost analysis was limited to operated patients. The first FNA yielded inadequate results in 28%, decreasing to 6% after 4 aspirations (n = 42). The other final classifications were: 76%, benign; 14%, follicular; 2%, suspicious; 1%, malignant (n = 7). Scintigraphy (99mTc) suggested a hyperfunctioning autonomous nodule (adenoma) in 12% and 3% of the inadequate and follicular subset, respectively. Surgery for diagnostic reasons (n = 105) yielded 24 malignancies (23%): in 47% of suspicious, 12% of the follicular, and in all with malignant FNA. Postoperative morbidity occurred in 14 (5 laryngeal nerve paralyses) with benign histology. Major cost drivers were surgery and hospitalization: mean costs per patient amounting to Euro 3.311 in case of benign histology. We conclude that current work-up is still unable to prevent unnecessary surgery for benign thyroid nodules. Thyroid scintigraphy proved most productive in the inadequate FNA category. Improvement of the diagnostic process using immunohistochemistry and/or imaging is needed from the patient's and society's perspective.