Objective: Diagnosis and grading of bladder cancers have a significant impact on treatment and prognosis. However, there are currently no very sensitive and specific immunohistochemical panels that can be used in the differential diagnosis of neoplastic lesions of the bladder and histomorphological findings are still the gold standard. We aimed to define the potential diagnostic importance of SPINK1, KRT17 and Laminin immunostaining in distinguishing neoplastic bladder lesions. Material and Methods: KRT17, SPINK1 and Laminin expressions were assayed in 141 tissue samples of non-neoplastic bladder mucosa (NBM) and neoplastic bladder lesions by immunohistochemistry. Results: KRT17 and SPINK1 are often expressed in tumoral tissues (86.2% and 68.7%, respectively). A statistically significant difference in KRT17 immunostaining was detected between the NBM and all seven neoplastic groups (p=0.03 to p<0.001). SPINK1 expression was significantly lower in NBM in comparison to neoplasms. Staining 2.5% or more of cells in tumor tissue with KRT17 distinguishes neoplastic lesions from nonneoplastic lesions with a sensitivity of 86.3% and a specificity of 100%. However, staining 12.5% or more of the cells in the tumor tissue with SPINK1 distinguishes neoplastic lesions from nonneoplastic lesions with a sensitivity of 62.6% and a specificity of 60%. Although both KRT17 and SPINK1 were stained in 60% of neoplasms, neither KRT17 nor SPINK1 staining was seen in 5.3% of neoplastic patients. Conclusion: Immunohistochemical panel consisting of KRT17, SPINK1 and Laminin can be used together with morphological findings for accurate diagnosis of bladder neoplasia.