Background Immunohistochemistry (IHC) for napsin A has been widely used to support a diagnosis of lung adenocarcinoma with high sensitivity. In this study, we evaluated immunoreactivity for napsin A in a broad spectrum of renal neoplasms by using tissue microarrays (TMA). Methods Duplicate TMA of 159 surgically excised renal neoplasms of various types were constructed. IHC for napsin A was performed on TMAs with appropriate positive and negative controls. Results Napsin A was expressed in Acquired cystic disease associated renal cell carcinoma (RCC) (2/2, 100.0%), chromophobe RCC (5/45, 11.1%), clear cell RCC (10/23, 43.5%), clear cell papillary RCC (9/19, 47.4%), metanephric adenoma (3/3, 100.0%), oncocytoma (13/23, 56.5%), and papillary RCC (31/37, 83.8%). Expression of napsin A was not seen in mucinous tubular and spindle cell carcinoma (0/1, 0.0%), TFE/MITF RCC 0/1, 0.0%), and urothelial carcinoma (0/6, 0.0%). Conclusions Napsin A is expressed in both common and rare sub-types of renal neoplasms with variable sensitivity. Based on our results, napsin A is not specific for lung adenocarcinoma. When a metastatic carcinoma of unknown primary is positive for napsin A, the differential diagnosis should include tumors of both renal and lung origin. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9558727831304717.