The accurate preoperative diagnosis of thyroid cancer continues to be a significant challenge for those individuals who present with nodular thyroid disease, particularly for tumors with indeterminate cytomorphological features by fine-needle aspiration biopsy. In an effort to develop improved diagnostic tools, a number of studies have investigated the discriminatory potential of many different RNA and protein molecules. However, no individual thyroid cancer biomarker has been found with sufficient sensitivity and specificity. Therefore, research focus has shifted to panels of multiple markers with the hope of improved performance and robustness. A panel comprised of GAL3, CK19 and HBME1 is by far the most studied to date and offers some improvement over individual marker performance alone. However, relatively few marker panels have been studied and their performances and application as diagnostic tests have not been consistently reported. We present a comprehensive review of molecular marker panel studies for thyroid tumors and current issues and challenges. In the future, studies evaluating larger numbers of biomarkers in large patient cohorts are required for the development and validation of a clinically applicable test.