Objective: To evaluate the relevance of microvessel density (MVD) and the angiogenic factors, vascular endothelial growth factor (VEGF, an important angiogenic factor in solid tumors) and thrombospondin-1 (TSP-1, a potent inhibitor of angiogenesis), to multifocality of renal cell carcinoma (RCC). Patients and Methods: Using immunohistochemistry the expression of CD34, TSP-1 and VEGF was assessed in 38 archival tissue specimens from 19 patients with unifocal RCC and 19 with multifocal RCC. Immunostaining results for VEGF was scored for the appropriate percentage of positive tumor cells and relative immunostaining intensity (score range 0-12). Only extracellular immunoreactivity was considered positive for TSP-1 and the same method was used to score the stromal staining. The microvessel density was measured by immunohistochemical staining Zn with anti-CD34 monoclonal antibody. Results: VEGF immunoreactivity greater than or equal to 1% was detectable in all unifocal and multifocal tumors. TSP-1 immunoreactivity was detected in 14 (73.7%) of 19 unifocal RCCs and in 16 (84.2%) of 19 rnuftifocal RCC specimens (p = 0.69). There were no statistically significant differences in the immunostaining intensity, percentage of immunopositive cells and the staining scores of VEGF and TSP-1 among the two groups. Additionally, there was no difference in MVD in multifocal and unifocal tumors. Conclusion: As there is no difference in MVD count, and expression of angiogenic factors (VEGF and TSP-1) in multifocal and unifocal tumors, multifocality of RCC is not determined by VEGF/TSP-1 expression. (C) 2003 Elsevier Science B.V. All rights reserved.