AIM: Wilms tumor (WT) usually shows a bi-phasic or tri-phasic morphology comprised of blastemal, stromal, and epithelial cells. Other biphasic renal tumors that can mimic WT may pose diagnostic dilemmas especially in preoperative needle biopsy samples. This tissue microarray study was designed to investigate the immunohistochemical features that may prove useful in the accurate diagnosis of WT in small biopsy samples. METHODS: Eight punches from each paraffin block of 45 cases of WTs were used to construct 5 tissue microarray blocks. Immunohistochemical reactions of blastemal, stromal, and epithelial cells of each core to a panel of 37 antibodies were evaluated. RESULTS: Blastemal elements expressed CD56 (22, 57%), CD57 (19, 55%), cytokeratin 22 (CK22) (12, 27%), and CK8 (9, 21%). Epithelial cells were stained mostly with CK22 (17, 94%), CK18 (12, 66%), CK8 (14, 70%), CD57 (10, 76%), CD56 (6, 43%), EMA (7, 44%), and CK19 (5, 25%). Stromal cells expressed SMA (21, 50%), actin (18, 48%), desmin (9, 20%), CD34 (7, 24%), CD57 (5, 18%), and CD56 (5, 15%). Only one case was positive for CK5/6, CK13, CK14, and CK20. Calretinin expression was seen in the stromal cells of 3 and placental alkaline phosphatase expression was observed in 1 case. All 3 components were negative for CK1, CK7, myoglobin, Myf-4, MyoD1, HMB45, chromogranin A, synaptophysin, Melan A, beta-HCG, alpha-HCG, alpha-Inhibin, renal cell carcinoma antigen, glycophorin A, PSA, and estrogen and progesterone receptors. CONCLUSIONS: CD56, CD57, CK22, CK18, CK8, EMA, SMA, and actin are useful markers for an accurate diagnosis of WT in small biopsy samples.