Glioblastoma (GB) is the most common malignant tumor of the brain. Most of these tumors are primary or GBs that manifest rapidly with initial presentations such as headache, new-onset epileptic seizure, focal neurological deficits, and altered mental status. The typical radiological features of GB include strong contrast enhancement, central necrosis, and edema with mass effect. Herein, we describe two cases of primary GB – two women aged 60 and 51 years who were diagnosed with GB 3.5 and 4 months, respectively, after their initial admission. These patients presented with right-sided headaches, and their neurological examination was within the normal limits. Their initial radiological investigations revealed no suspicious lesions, either on T1-weighted or T2-weighted magnetic resonance (MR) images. The 60-year-old patient was readmitted with persistent headache, and her T1-weighted MR images revealed a well-demarcated mass lesion in the right temporal lobe with strong contrast enhancement. Moreover, the T2-weighted MR images revealed closed sulci and swollen midline structures because of edema. The 51-year-old patient was readmitted with persistent headache, and her MR image revealed a mass lesion with heterogeneous contrast enhancement and necrosis on T1-weighted images and hyperintense areas with severe edema on T2-weighted images. The patients underwent craniotomy and gross total tumor resection. Notably, in both cases, the lesions were pathologically diagnosed as GB. Therefore, it should be borne in mind that only persistent headache could be a sentinel sign of GB before it becomes radiologically visible, thereby emphasizing the need for follow-up imaging studies at short intervals.