Background: Multinodular goiters (MNG) have recently been shown to have an incidence of cancer that approaches that of solitary thyroid nodule. However, fine needle aspiration (FNA) of a MNG is limited due to the presence of multiple nodules. Therefore we sought to identify risk factors for malignancy in patients with MNG. Methods: A total of 1791 consecutive patients underwent thyroidectomy at a single academic institution between May 1994 and December 2009. Of these, 838 patients had a MNG, which we defined as ≥2 nodules on preoperative ultrasound. The medical records of these patients were reviewed and analyzed. Results: A final pathologic diagnosis of malignancy was found in 260 of 838 (31%) of MNG patients. Of the 260 patients with malignancy, 113 (44%) had a focus of cancer <1 cm. Of the patients with malignancy on final pathology, preoperative FNA detected only 46% (n = 120). Of the 140 cancers not recognized preoperatively, 61 (44%) were >1 cm in size. On univariate analysis risk factors for malignancy were younger age and male gender. Patients with malignant nodules also had smaller nodules, smaller thyroids, and fewer nodules than those patients with benign findings on pathology. On multivariate analysis all predictors remained independently associated with malignancy with the exception of thyroid weight. Conclusion: Risk factors for malignancy in a MNG included male gender, younger age, fewer nodules, and smaller nodule size. The low predictive value of FNA in our population suggests there needs to be better ways to predict malignancy in patients with MNG. Therefore, these clinical risk factors should be considered when consulting patients with MNG in regards to their risk of malignancy. © 2012 Elsevier Inc. All rights reserved.