With diagnostic stereotactic biopsies in astrocytoma sometimes false results will be encountered. A false positive result is defined as a histological diagnosis which is afterwards proved to be untrue. Although this happens very seldom (1-2%) in characterizing the tumor type (e.g. astrocytoma versus lymphoma), there is a probability of undergrading in malignant astrocytomas due to regional heterogeneity in malignancy grade. The issue of 'sampling error' has been addressed by many authors. It was shown that undergrading in astrocytomas is a likely event in fibrillar astrocytomas that often show geographically distinct areas of well and poorly differentiated elements. In a recent study on histological grading versus genetic characterization of heterogeneous astrocytomas we published that low-grade areas within high-grade malignant astrocytomas have already the genetic features of high-grade malignancy. Therefore, particularly in stereotactic biopsies which contain relatively small samples of tumor tissue, this fact is of paramount importance. Undergrading may lead to withholding radiotherapy from the patient and to falsification of long-term survival results in series of so-called low-grade astrocytomas. We like to stress the importance of taking biopsies from different parts of the tumor, especially from parts with different density enhancement to contrast with CT scanning, and will discuss the technical advancements made in the genetic grading of astrocytomas. Particularly loss of heterozygosity of chromosome 10 and eventually amplification of the EGFR indicate a high grade of malignancy.