Abstract BACKGROUND Hot‐spot microvessel density (MVD) and vascular patterns have been reported as histopathologic factors that influence prognosis in retrospective series of malignant gliomas. To investigate clinical utility, the authors systematically studied observer agreement on MVD and vascular patterns and the influence of repeatedly assessed data on patient outcomes in 2 independent glioblastoma series. METHODS MVD and vascular patterns were assessed retrospectively by 5 observers in 1) a retrospectively compiled glioblastoma series that included 110 patients and 2) a glioblastoma series that included 233 patients who were treated within a randomized trial. MVD was determined in the field of greatest density (“hot‐spot”). Predominantly classic or bizarre vascular patterns were determined by using a previously defined algorithm. RESULTS Observer agreement on MVD was highly variable (range of κ values, 0.464‐0.901). The worst observer agreement was achieved when both the selection of hot‐spots and MVD counts were performed independently. Survival analysis did not show a consistent association between repeatedly assessed MVD and patient outcome. Observer agreement on vascular patterns was poor (κ = 0.297). Survival analysis did not show a consistent association between repeatedly assessed vascular patterns and patient outcome. CONCLUSIONS Observer agreement on hot‐spot MVD and vascular patterns in patients with glioblastoma was poor in independent assessments. MVD and vascular patterns were not associated consistently with patient outcome. Based on these findings, the authors concluded that poor observer agreement limits the clinical utility of histopathologically assessed hot‐spot MVD and vascular patterns as prognostic factors in patients with glioblastoma. Improved methodologies for morphologic assessment of glioblastoma vascularization need to be identified. Cancer 2006. © 2006 American Cancer Society. The results of this investigation revealed that poor observer agreement limits the clinical utility of histopathologically assessed hot‐spot microvessel density and vascular patterns as prognostic factors in patients with glioblastoma. Improved methodologies for morphologic assessment of glioblastoma vascularization need to be identified.