Objective Ultrasound-guided fine-needle aspiration (FNA) biopsy is the primary method of evaluating thyroid nodules. Up to one-third of FNA results are reported to be of indeterminate cytology, which carries a 25% malignancy risk. Most of these patients are referred for diagnostic surgery, which results in many unnecessary interventions. We implemented an FNA protocol combining expert thyroid cytopathology and molecular testing of indeterminate lesion in our community practice. This study is a report of the outcomes from this protocol as compared with historical data in the same setting over a similar period. Study Design Case series with planned data collections and retrospective chart reviews. Setting A large community-based practice with multiple satellite offices. Subjects and Methods A total of 264 thyroid nodules (196 patients) were evaluated under the new protocol from January to December 2014, and data were collected in a prospective manner. Historical data for a similar period (2012), obtained by chart review, included 164 nodules (134 patients) biopsied in a hospital setting by a number of radiologists, with cytologic interpretations completed by community-based pathologists. Statistical analyses included (2) and Fischer's exact tests. Results Based on the new protocol, the rate of indeterminate lesion diagnosis was reduced from 24% to 10% (P = .006) and the rate of diagnostic surgery from 24% to 6% (P < .001). Of the patients who underwent diagnostic surgery, 58% had evidence of malignancy, as compared with 12% in our previous experience (P = .04). Conclusion Expert cytopathologic analysis combined with molecular testing of indeterminate FNA samples significantly reduced unnecessary operations.