Introduction: Thyroid cancer is the most common endocrine malignancy. Although typically well controlled with surgery and radioactive iodine treatments, some patients suffer from recurrent disease that can be fatal. For some of these patients current therapies fail and thus new treatment modalities are needed. Immunotherapy is a promising approach for treating cancer in general but the way in which the immune system interacts with thyroid cancer is poorly characterized or understood. A better understanding of this interaction should help guide efforts to use the immune system to treat thyroid cancer. ? Purpose: Characterize immune responses to thyroid tumors in patients experiencing different degrees of disease progression. ? Approach: Design and initiate a retrospective study analyzing archived papillary thyroid cancer samples regarding lymphocyte subtype infiltration by immunohistochemistry staining and compare to disease progression. ? Results: Paraffin-preserved samples of thyroid tumors were obtained from 43 patients. The samples were sectioned, stained, and evaluated for the presence of cells expressing lymphocyte markers CD3, CD8, CD16, CD68, and FoxP3. No significant differences were found in the number of CD8?, CD68?, CD16? and FoxP3? regulatory T cells with respect to both age and lymph node status in papillary thyroid cancer. A decreasing number of CD16? cells significantly correlated with an increase in age. Moreover, there were generally a greater number of effector CD8? cells relative to FoxP3 regulatory cells across the patient population. ? Conclusions: The results support the hypothesis that there is an active immune response to papillary thyroid carcinomas that may relate to disease prognosis. The age and lymph node status does not appear to predict characteristics of the immune response. The correlation between NK cells and prognosis may be worth further exploring as NK cells are associated with tumor rejection and limited disease recurrence.