The aim of this study is to identify immunohistochemical (IHC) markers that can reliably separate schwannoma (SCHW) and fibroblastic meningioma (FM). We selected 106 cases of intracranial SCHW (n = 56) and FM (n = 50) and constructed a tissue microarray (TMA) of core diameter of 1.0 mm from archival formalin-fixed paraffin-embedded tissue. A TMA-IHC was performed using 14 antibodies. After IHC staining, 98 cores were found suitable for evaluation. The IHC staining was scored as 0-2+ (0, negative; 1+, weak and/or focal 2+ strong and/or diffuse positive). A discriminant analysis (DA) (Wilks'Lambda test) was performed to assess the relative importance of these biomarkers in classifying the two groups FM and SCHW. It showed that WT-1 (Wilks'λ 0.085, p < 0.001), EMA (Wilks'λ 0.253, p < 0.001), S100 (Wilks'λ 0.487, p < 0.001), Claudin-1 (Wilks' λ 0.57, p < 0.001) and Ezrin (Wilks'λ 0.656, p < 0.001), SPARC (Wilks'λ 0.751, p < 0.01), NP-Y (Wilks'λ, 0.819, p < 0.001) and EGFR (Wilks'λ 0.845, p = 0.026) were some of the statistically significant markers that discriminated SCHW and FM. For sensitivity and specificity for SCHW the significant markers [Area under the curve (95% CI), p-value] by ROC analysis were WT-1 [0.990(0.000, 1.000), <0.001], S100 [0.880(0.808, 0.951), <0.001] while for diagnosing FM the most sensitive and specific markers were EMA [0.957(0.914, 1.000), <. 001], Claudin-1 [0.857(0.782, 0.932), <0.001] and ezrin [0.792(0.700,0.884),<0.001]. WT-1, Claudin-1 and Ezrin may be potentially useful immunohistochemical adjuncts to EMA and S100 that differentiate SCHW from FM.