Abstract Headaches in cancer patients can indicate serious conditions such as intracranial metastases, intracranial hypertension, meningeal carcinomatosis, or treatment side effects. Clinically, these headaches often present progressively and are accompanied by neurological symptoms such as focal deficits, seizures, or altered mental status. They may worsen with maneuvers that increase intracranial pressure and often have a nocturnal predominance, showing limited response to conventional analgesics. This underscores the importance of early diagnosis using imaging techniques, such as magnetic resonance imaging with gadolinium, alongside a multidisciplinary approach that includes neurosurgical interventions, radiotherapy, or chemotherapy, along with effective symptomatic control to enhance patients’ quality of life. In this context, we present the case of a 21-year-old patient with stage IV nonseminomatous metastatic testicular cancer involving the central nervous system. Despite receiving oncological treatment, including chemotherapy and resection of a brain lesion, the patient developed severe headaches that were refractory to standard analgesic therapy. A diagnostic block of the sphenopalatine ganglion (SPG) was performed using transnasal bupivacaine, followed by chemical neurolysis of the right SPG with bupivacaine and 100% alcohol under fluoroscopic guidance. This intervention resulted in significant and sustained pain relief, greatly improving the patient’s quality of life. This case highlights the need for further investigation into interventional strategies for managing secondary headaches in cancer patients.