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Background and purpose: Multinodular goiter is a benign enlargement of thyroid gland and papillary thyroid carcinoma is the most common type of thyroid cancer. Today, immunohistochemical markers can be used in diagnosis and prognosis of tumors. The aim of this study was to compare the expression of CD117 in multinodular goiter and papillary thyroid carcinoma and its association with prognostic factors. Materials and methods: In this cross-sectional study, samples of thyroid tissue from 60 multinodular goiter and 60 papillary thyroid carcinoma cases who underwent thyroidectomy in Tehran Mostafa Khomeini Hospital during 2011-18, were evaluated for CD117 expression via immunohistochemistry. The expression intensity was scored 0-3. Results: CD117 was expressed in all samples with generally lower expression scores in malignant samples: 95% and 5% of malignant cases showed scores 1 and 2, respectively. Almost 52% and 48% of benign cases showed score 1 and scores 2 and 3, respectively (P<0.05). Increased CD117 expression was associated with decreased lymph node involvement and increased tumor size (P<0.05), but there was no significant relationship between this marker and other prognostic variables (P=0.081). Conclusion: There are contradictory findings on the relation between CD117 expression and prognostic factors in malignant cases, therefore, further studies are recommended to clarify the association.