Purpose: High-grade glioma (HGG) is a common form of malignant primary brain cancer with poor prognosis. The diffusive nature of HGGs implies that tumor cell invasion of normal tissue extends several centimeters away from the visible gross tumor volume (GTV). The standard methodology for clinical volume target (CTV) delineation is to apply a 2-to 3-cm margin around the GTV. However, tumor recurrence is extremely frequent. The purpose of this paper was to introduce a framework and computational model for the prediction of normal tissue HGG cell invasion and to investigate the agreement of the conventional CTV delineation with respect to the predicted tumor invasion. Methods and Materials: A model for HGG cell diffusion and proliferation was implemented and used to assess the tumor invasion patterns for 112 cases of HGGs. Normal brain structures and tissues as well as the GTVs visible on diagnostic images were delineated using automated methods. The volumes encompassed by different tumor cell concentration isolines calculated using the model for invasion were compared with the conventionally delineated CTVs, and the differences were analyzed. The 3-dimensional-Hausdorff distance between the CTV and the volumes encompassed by various isolines was also calculated. Results: In 50% of cases, the CTV failed to encompass regions containing tumor cell concentrations of 614 cells/mm3 or greater. In 84% of cases, the lowest cell concentration completely encompassed by the CTV was & GE;1 cell/mm3. In the remaining 16%, the CTV overextended into normal tissue. The Hausdorff distance was on average comparable to the CTV margin. Conclusions: The standard methodology for CTV delineation appears to be inconsistent with HGG invasion patterns in terms of size and shape. Tumor invasion modeling could therefore be useful in assisting in the CTV delineation for HGGs.