Objective To discuss the clinical characteristics and early diagnosis of patients with cerebral venous sinus thrombosis (CVST) mainly presented as isolated headache. Methods The clinical data of 6 patients with CVST presented as isolated headache were collected, and they were hospitalized in the Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine from Jan. 2012 to Dec. 2016. The clinical features, D-dimer level, non-contrast cranial CT imaging and cranial contrast-enhanced magnetic resonance venography (CE-MRV) imaging of the patients were retrospectively analyzed. Results All the 6 patients were young, including 5 males and 1 female, with acute headache as a single clinical manifestation. The degrees of the headache were moderate to severe, and continuously became worse. The headaches were located in the frontotemporal and occipital areas, and the pains were mainly distending and throbbing. The levels of D-dimer were increased in 4 cases and normal in 2 cases. The non-contrast cranial CT imaging showed that the densities of transverse sinus were increased in 5 patients. CVST was finally confirmed by cranial MRI+CE-MRV in all the patients, and the most involved sinuses were transverse sinus and sigmoid sinus. All the 6 patients were relieved of headache after anticoagulant therapy, and the prognosis was good. Conclusion Patients with CVST mainly presented as isolated headache are extremely rare. Therefore, we need to pay attention to the patients with newly progressive isolated headache in clinc. These patients need early diagnosis by cranial MRI+CE-MRV to avoid misdiagnosis even if the D-dimer levels are normal, and then they can have good outcomes after early diagnosis and treatment.