KISS1 protein and KISS1 receptor form a system that mainly promotes suppression of metastasis in various forms of cancer. We studied the relationship between KISS1/KISS1R expression and tumor progression in differentiated thyroid cancer (DTC).Thirty-three patients diagnosed with DTC were included in the study. Immunohistochemical cytoplasmic expression was evaluated for KISS1 and cytoplasmic/membranous expression for KISS1R in thyroid cancer tissues.KISS1 expression was significantly higher in tumors with extrathyroidal invasion and advanced stage. KISS1R expression showed a statistically significant, moderate negative correlation with tumor size.Increased expression of KISS1 is possibly acquired to prevent further tumor invasiveness and formation of local or distant metastasis. It appears that malignant cells in DTC express increased levels of KISS1 as the tumor invades extrathyroidal tissues. Decreased expression of KISS1R seems to attenuate signaling of the KISS1/KISS1R system, possibly leading to tumor growth.