Introduction and importanceIn adults, glioblastomas account for approximately 12–15 % of primary intracranial neoplasms. In current standard-of-care treatment, glioblastomas have a 5-year survival rate of ~7.5 % and a median survival of ~15 months. Glioblastoma exhibits a highly variable imaging appearance, but the thick and irregular ring enhancement surrounding a necrotic core with infiltrative growth is the most prevalent imaging pattern. Glioblastoma with a cystic component (also known ascystic glioblastoma) is a rare presentation that can be misleading and often mistaken for other cystic brain lesions.Case presentationIn this report, we present a case of a 43-year-old woman who presented to the emergency department with a 2-month history of progressive neurologic manifestations that was attributed to a right-sided cystic brain lesion detected on routine imaging studies, which was later characterized as a cystic glioblastoma based on specific imaging and molecular studies.Clinical discussionWe highlight the importance of combining radiological and molecular modalities with clinical suspicion for a better characterization of cystic brain lesions and including glioblastoma in the list of potential diagnoses. Furthermore, we provide a comprehensive, evidence-based review of the entity of cystic glioblastoma and how the existence of the cystic component might affect the management and the overall prognosis.ConclusionSeveral characteristics make cystic glioblastoma unique. However, it is also capable of mimicking other benign cystic brain lesions, delaying definitive diagnosis and hence the most appropriate management plan.