Objective: To identify novel prognostic risk factors and compare them with other known prognostic risk factors in follicular cell derived thyroid carcinoma (FDTC) with distant metastases. Methods: A retrospective review was conducted of adult patients with metastatic FDTC seen at a tertiary care center between January 1990 and December 2010. A 15-year Kaplan-Meier survival estimate was created for overall survival (OS) and cancer-specific survival (CSS). Hazard ratios (HR) and P values from Cox proportional hazard models were used with a 95% confidence interval (CI). Results: There were 143 patients (60.1% male, 39.9% female), of whom 104 (72.7%) patients had papillary, 30 (21.0%) had follicular, 5 (3.5%) had poorly differentiated, and 4 (2.8%) had Hürthle cell cancers. Median length of follow-up was 80.0 months (range 1.0-564.0). The 15-year mortality rate was 32.2% and cancer-specific mortality was 25.2%, with OS and CSS having the same risk factors. Lung was the most common site of metastases in 53 patients (37.1%), and patients with pleural effusions had significantly lower CSS (HR = 5.21, CI = 1.79-15.12). Additional risk factors for a decreased CSS included: older age upon diagnosis (>45 years, HR = 4.15, CI = 1.43-12.02), multiple metastatic locations (HR = 3.75, CI = 1.32-10.67), and incomplete/unknown tumor resection (HR = 2.35, CI = 1.18-4.67). Conclusion: This study is the first to demonstrate that pleural effusion is a poor prognostic sign in patients with FDTC with distant metastases and compare this risk with other accepted prognostic variables.