Background: Vascular endothelial growth factor (VEGF) is a key molecular driver of angiogenesis and vascular permeability and is expressed by a wide variety of neoplasms. Although blood VEGF concentrations have been quantified in intracranial tumors of dogs, cerebrospinal fluid (CSF) VEGF concentration might be a more sensitive biomarker of disease.Objective: Concentrations of VEGF in CSF are higher in dogs with central nervous system (CNS) neoplasia compared to those with meningoencephalomyelitis and other neurologic disorders.Animals: One hundred and twenty-six client-owned dogs presented to a veterinary teaching hospital.Methods: Case-control study. Cerebrospinal fluid was archived from dogs diagnosed with CNS neoplasia and meningoencephalomyelitis. Control dogs had other neurological disorders or diseases outside of the CNS. A commercially available kit was used to determine VEGF concentrations.Results: Detectable CSF VEGF concentrations were present in 49/63 (77.8%) neoplastic samples, 22/24 (91.7%) inflammatory samples, and 8/39 (20.5%) control samples. The VEGF concentrations were significantly different between groups (P < .0001), and multiple comparison testing showed that both neoplastic and inflammatory groups had significantly higher concentrations than did controls (P < .05), but did not differ from each other. Gliomas and choroid plexus tumors had significantly higher VEGF concentrations than did the control group (P < .05).Conclusions and Clinical Importance: Cerebrospinal fluid VEGF concentrations may serve as a marker of neoplastic and inflammatory CNS disorders relative to other conditions.