This study analyzed the expression of angiogenic factors in retinoblastoma tumors with high-risk features (HRF) compared to those without. The results showed that HRF tumors expressed significantly higher levels of VEGF and VEGFR2 than non-HRF tumors. Staining indicated the VEGF was secreted by tumor cells. Neovascularization was also higher in the iris for HRF tumors. The increased expression of these angiogenic factors in HRF tumors correlated with higher expression of the stem cell marker SOX2, suggesting HRF tumors have more stem-like properties. The conclusions were that HRF tumors may regulate their invasiveness through a VEGF feedback loop, and that temporal expression of VEGF receptors should be considered. Anti