The co-occurrence of astrocytomas and multiple sclerosis (MS) is an uncommon, but well reported phenomenon [1, 2]. Our group recently reported the genetic features of eight well characterized patients with co-existent glioma and multiple sclerosis and found no unique genetic features in tumors from MS patients . None of those cases showed a definitive relationship between the tumor and a demyelinative lesion. However, since the 1980s, there has been speculation that chronic gliosis in demyelinative plaques may predispose to secondary induction of a glial neoplasm . Malmgren et al. reviewed 25 cases in the literature, specifically looking for features that might link the two disorders: contiguity of glioma and MS plaques, neoplastic transformation of astrocytes within MS plaques, multicentricity of gliomas, increased proportion of an astrocytic type of glioma, temporal sequence of MS and glioma, possible increased rate of gliomas in MS patients, and a biological plausibility of a causal relationship . They concluded that ‘‘there currently is no reason to believe that the lesions of multiple sclerosis promote the development of gliomas’’ . Herein, we report a case of diffuse low-grade astrocytoma with strong IHC expression for both IDH1 and p53 arising at the edge of a definitive small ovoid demyelinative plaque, fulfilling a major criterion of Malmgren et al., and suggesting that, at least in some cases, chronic gliosis in demyelinative plaques may result in neoplastic astrocytic transformation.