Background: Transformation to glioblastoma following recurrent epidermoid cyst resection has not been reported. Chronic inflammation can underlie malignant transformation of epidermoid cysts. Astrogliosis following repeated resections may have induced the rare transformation to glioblastoma. Clinical presentation: A patient presenting with left lower extremity weakness was found to harbor a parietal mass lesion. Histopathology demonstrated an epidermoid cyst. Following multiple re-resections, an intra-axial mass was discovered within the operative bed, confirmed as glioblastoma. Conclusion: This is the first report of glioblastoma associated with a resected epidermoid cyst. Subsequent to resection, the chronic inflammatory milieu propagated by astrogliosis is thought to have induced malignancy. The progression to glioblastoma draws attention to neoplastic transformation in the context of recurrent epidermoids.