Abstract Recent reports have shown significant correlation between Fuhrman nuclear grade of renal cell carcinoma (RCC) and patient survival. However, no one specific gene alteration has yet been described to account for this correlation. This study investigated the expression of the insulin-like growth factor-I receptor (IGF-IR) in RCC and correlated the results to the tumor Fuhrman nuclear grade. Formalin-fixed, paraffin-embedded sections from 68 cases of RCC were stained using the immunohistochemical avidin-biotin-peroxidase method. An anti-human IGF-IR rabbit polyclonal antibody was used. The stains were semiquantitatively evaluated using the Allred score system, assessing intensity of stain and percentage of positive tumor cells. Statistical analysis was performed using the Kruskal-Wallis test. Strong and diffuse cytoplasmic IGF-IR stain (Allred score 7 to 8) was identified in 25 of 25 (100%) of grade 3 and 4 RCCs. Grade 2 RCCs had a median IGF-IR Allred score of 4. Ten of 10 (100%) grade 1 RCCs were negative. Even in the positive high-nuclear-grade tumors, areas of low nuclear grade, when present, were IGF-IR negative. Statistical analysis using the Kruskal-Wallis test demonstrated significant correlation between increasing Fuhrman nuclear grade and increasing IGF-IR Allred score ( P <0.0001). Thus we report the novel finding of significant statistical correlation between IGF-IR protein expression and Fuhrman nuclear grade of RCC, and consequentially with patient survival.