Renal cell carcinoma, unclassified (RCC-U), is a heterogenous group of tumors that do not fit in any recognized histologic types. Immunohistochemical studies are frequently used to characterize these tumors. Herein, we sought to investigate the immunophenotypes of 300 cases of RCC-U. The cases were morphologically classified into three groups: oncocytoma/chromophobe renal cell carcinoma-like -Group 1; clear cell renal cell carcinoma-like – Group 2; and others (i.e., papillary renal cell carcinoma-like/collecting duct-like/pure sarcomatoid) – Group 3. Male-to-female ratio was 1.4. Most cases (168, 66%) were Group 1. Group 3 was associated with larger tumor size, advanced stage, and frequent lymph node metastases. The most commonly used immunohistochemical stains were CK7 (n=270; 89.5%), vimentin (n=186, 82%), CD10 (n=181; 59.9%), and AMACR (n=162; 54%). Pancytokeratin (79/101; 78.2%) and PAX8 (54/61; 88.5%) were diffusely positive in most cases, followed by AMACR (69/117; 59%). CD117 was positive in 53/118 cases (45%). RCC-U is a morphologically and immunophenotypically heterogenous group of tumors, comprehensive work-up is needed before rendering the diagnosis.Copyright © 2020. Published by Elsevier Inc.