A 45-year-old man was admitted with severe headache and left-sided weakness, which worsened over 1 week. Brain imaging revealed a small lesion close to the sagittal sinus in the right frontal lobe with severe perilesional edema and showed enhancement on both CT and MRI obtained with contrast. Serological findings were positive for toluidine red unheated serum test (TRUST) positivity and Treponema pallidum particle agglutination assay. The patient was first suspected of having a malignant brain tumor and subsequently received emergency craniotomy. Brain biopsy suggested a diagnosis of syphilitic cerebral gumma; meanwhile the postoperative CSF TRUST titer was positive, and the patient’s improvement with high-dose intravenous aqueous crystalline penicillin further supported this etiology. Finally, the lesion on the right frontal lobe had disappeared during the follow-up imaging examination and the myodynamia of the left limbs gradually improved. The authors recommend that diagnostic penicillin treatment should be first implemented. When a patient’s history, clinical manifestations, syphilis serology, CSF examination, and other physiological changes indicate a diagnosis of syphilitic cerebral gumma, there is no doubt that surgery should be performed in patients with acute intracranial hypertension, but unnecessary craniotomy should be avoided as far as possible.