Several blood biomarkers have been established for the early diagnosis, screening and follow-up of non central nervous system cancers. However, there is lack of knowledge on biochemical blood alterations in brain tumor patients. In this study, we prospectively collected blood plasma samples of 105 adult brain tumor patients with diffuse low-grade glioma (World Health Organization (WHO) II, n = 7), anaplastic glioma (WHO III, n = 10), glioblastoma multiforme (WHO IV, glioblastoma multiforme (GBM)) (n = 34), meningioma (WHO I, n = 8), atypical meningioma (WHO II, n = 5), and intracerebral metastasis (ICM; n = 41). In each case, we measured plasma concentrations of neuropeptide Y, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, placental growth factor (PlGF), S100B, secretagogin, interleukin 8, and glial fibrillary acidic protein (GFAP) using enzyme-linked immunosorbent assay. Plasma marker concentrations were correlated to patient parameters including neuropathological diagnosis and neuroradiological features. Most of the markers were detectable in all diagnostic categories in variable concentrations. GFAP plasma detectability was strongly associated with a diagnosis of GBM (p < 0.001). Plasma GFAP and plasma placental growth factor showed promising moderate potential in the differential diagnosis of unifocal GBM versus unifocal supratentorial ICM (area under the curve = 0.73, p < 0.05). To summarize, our data show that none of the investigated markers is suitable to substitute histological diagnosis. However, measurement of circulating GFAP and PlGF may support neuroradiological differential diagnosis of GBM versus ICM.