Purpose To evaluate the potential role of immunohistochemical changes in stanniocalcin 1 (STC1) and stanniocalcin 2 (STC2) expressions in papillary thyroid cancer (PTC) tissues in the disease's diagnosis and to investigate their relationship with classical clinicopathological prognostic factors. Methods The study included 100 patients with PTC. Normal thyroid tissue adjacent to the tumor was taken as the control group. Clinicopathological prognostic features at the time of diagnosis of patients were recorded. STC1 and STC2 expressions of tumor tissue and adjacent normal tissue were determined immunohistochemically. Results The sensitivity of STC1 in the diagnosis of PTC was 93%, the specificity was 94%, positive predictive value (PPV) 93.9%, and negative predictive value (NPV) 93.1%. It was determined that the STC1 staining score in tumor tissue was positively correlated with the disease TNM stage score (r = 0.259, p = 0.009) and the increase in STC1 staining score were independent risk factors that increased the risk of lymph node metastasis (R-2 = 0.398, p < 0.001). While 21% of the tumor tissues were stained with STC2, none of the normal thyroid tissues adjacent to the tumor tissue showed any staining with STC2. No correlation was found between STC2 immunohistochemical staining of tumor tissue and clinicopathological risk factors for the disease. Conclusion Increased STC1 expression in thyroid lesions may be helpful in diagnosing PTC. In addition, since increased STC1 expression in PTC tissues is associated with the risk of lymph node metastasis, it may be an efficient marker for predicting the prognosis of the disease.