To develop a reliable immunohistochemical marker panel differentiating between the three most common renal cell carcinoma (RCC) subtypes without inclusion of histomorphologic criteria we investigated protein expression of vimentin, glutathione S-transferase alpha (GST-α), CD10, CD117 (C-KIT), carbonic anhydrase 2 (CAII), parvalbumin, alpha-methyl-CoA-racemase (AMACR), and cytokeratin-19 (CK 19) in 65 age and stage matched trios of clear cell carcinoma, papillary renal carcinoma and chromophobe renal carcinoma using tissue microarrays. All markers displayed significant differential expression among the subtypes (p < 0.001) except CAII (p = 0.192). According to positive (LR+) and negative (LR-) likelihood ratio, six markers (CD10, GST-α, AMACR, CK19, C-KIT and arvalbumin) demonstrated acceptable or good values to detect certain subtypes of RCC, but failed in terms of ruling out the respective subtypes. Based on the individual performance of these six markers, we combined them and reviewed each single case: LR+ for detection of clear cell RCC considerably increased by application of the six marker panel, but did not exceed 10. LR- was still >0.1; in case of papillary RCC LR+ rose beyond 10, but LR- remained >0.1. LR+ for recognition of chromophobe RCC rose far beyond 10, but LR- remained >0.1. Thus, the panel can reliably recognize two main RCC subtypes without inclusion of histomorphologic features. Further improvement is needed for consistent detection of clear cell RCC and for dependably ruling out all three main subtypes as well as identification of rare variants and benign lesions like oncocytoma.