BACKGROUND: Renal cell carcinoma (RCC) with multinucleated giant cells has been reported in the literature. Different types of multinucleated giant cells have been described, including the osteoclast-like giant cells, rhabdoid cells, syncytial giant cells and tumor multinucleated giant cells. RESULTS: We describe a unique case of a clear cell RCC with extensive giant cell component. Tumor giant cells were arranged in an alveolar pattern and formed more than 50% of the tumor. The rest of the tumor was a classic clear cell renal cell carcinoma. A rhabdoid component was also focally seen. The immunohistochemical profile of the giant cells showed positivity for RCC, vimentin and, very focal positivity for cytokeratins, and negatively for CD68. A traditional spindle cell sarcomatoid component was not seen. The patient had advanced disease at presentation with metastasis to peri-aortic lymph nodes. CONCLUSION: Giant cells can rarely constitute a major component of renal cell carcinoma and it is not clear if these represent a sarcomatoid component or merely a higher grade of the epithelial component. These cells may have different immunohistochemical profiles in different cases and may therefore be of different derivation. This may necessitate the revision of current classification schemes for renal cell carcinoma. It is also not clear how the presence of the various types of giant cells in renal cell carcinoma and their amount affects the clinical outcome.