Canine non-Hodgkin's lymphoma (NHL) is considered to be a good animal model for its human counterpart; nevertheless, comparative data on neo-angiogenesis are completely lacking. The aim of this study is to investigate the levels of serum vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) 2 and 9 in lymphoma-affected dogs. Circulating levels of VEGF and both MMP 2 and 9 activities significantly correlate with the WHO sub-stage b prognostic factor; moreover, VEGF at admission have an independent influence on the length of the disease free interval. As in humans, serum VEGF concentration and most likely also MMPs plasma activity have prognostic value in canine NHL spontaneous model.