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Background & objective There is currently inadequate information about the expression of immunohistochemical markers in pediatric tumors. Paired box genes 2 and 8 (PAX2 and PAX8) genes have an essential role in kidney organogenesis. This study aimed to investigate the IHC expression of PAX2 and PAX8 in Wilms tumor. Such study would be helpful in diagnosis and possibly in differentiation of this tumor from other mimics, especially in those of poorly differentiated type in small needle biopsy specimens. Methods We performed a cross-sectional study on 45 Wilms tumor cases referred to Bahrami pediatric hospital between 2005 and 2015. Demographic data were collected from medical documents. Sections from related paraffin blocks were provided by the tissue microarray method, and immunohistochemical (IHC) staining was done for PAX8 and PAX2. Results The mean tumor size was 9.98±4.95 cm. Favorable histology was seen in 84.4% of samples. PAX2 was expressed in 41 cases (91.1%), and PAX8 in 37 patients (82.2%). PAX2 and PAX8 expression was mostly seen in both blastemal and epithelial components (77.8% and 66.6%), respectively. Tumors with favorable and unfavorable histology did not significantly differ in PAX2 and PAX8 expression (P=0.637). We found a statically significant relationship between PAX8 expression and tumor size (P=0.033). Conclusion PAX2 and PAX8 markers might helpful in diagnosis of Wilms tumor and may differentiate it from other histologically similar kidney tumors. PAX8 expression may be associated with larger tumor size. Tumors with favorable and unfavorable histology may not be different in PAX2 and PAX8 expression.