BACKGROUND: It is well recognized that the histology of renal cell carcinoma (RCC) is often heterogeneous. It is also believed that the prognosis of patients with large tumors is generally poorer than those with small tumors. However, there has been no detailed study on changes in histological features of RCCs associated with tumor growth. This study was conducted to investigate whether there are any specific histological changes related to tumor size and to study the prognostic value of histological parameters in RCCs. METHODS: The presence or absence of each histological component (3 cell types and 5 histological architectures) was investigated in 110 RCCs. The tumor size-associated changes in the histological composition of the RCCs were evaluated, and the prognostic significance of the histological parameters was analyzed using univariate and multivariate analysis. RESULTS: The percentage of RCCs with multiple cell types increased with tumor size, whereas increases in multiplicity were not as prominent in the histological architectures. Several characteristic changes, however, were observed in both cell types and architectures. RCCs with a pure clear cell, pure alveolar pattern or cystic architectural pattern decreased, while those with granular or spindle/pleomorphic cell types, or papillary or solid architectural patterns increased with tumor size. A univariate analysis revealed that a clear cell type and an alveolar or cystic architectural pattern were associated with a better prognosis, while spindle/pleomorphic cells and a solid architecture pattern correlated with a poorer prognosis. Multivariate analysis of cell types and architectures showed, however, that only the presence of spindle/pleomorphic cell types and a solid architecture were independent prognostic variables. CONCLUSION: The histological composition of RCCs varied according to the size of the tumor. Sarcomatous components increased with tumor size and were independently associated with a poor prognosis. Further study is warranted to correlate specific genetic alterations with tumor growth-related histological changes in RCCs.