Background Core needle biopsy (CNB) is a relatively new technique for the diagnosis of thyroid nodules, and there are currently no large clinical series available. CNB results from 3000 cases are presented in this article. Methods A spring-loaded 20-gauge needle was used for CNB under local anesthesia and ultrasonography guidance for 3000 patients with nodular goiter (584 males, 2416 females, mean age: 48.5). One physician performed all biopsy procedures without conducting on-site pathological examinations. Results There were non-diagnostic 22 (.7%), benign 2620 (87.4%), atypia of undetermined significance and/or, follicular lesion of undetermined significance 90 (3%), follicular neoplasms and/or suspicious for follicular neoplasm 53 (1.7%), suspicious for malignancy 160 (5.4%), and malignant 55 (1.8%) cases. The CNB procedure was repeated in 19 non-diagnostic cases, and 17 of these patients were benign and two had malignancy. Thyroidectomy was performed on patients who had malign CNB results. All final pathology reports, except for one, were malignant for the patients who had malignant CNB results. The specificity and the sensitivity of CNB were found to be 99.9% and 100%, respectively. There were no serious complications. Conclusion In thyroid nodules, core needle biopsy is a highly sensitive, specific, and reliable method that could be performed by a single physician. It does not require on-site pathological analysis and has a low incidence of complications and non-diagnostic rates.