We prospectively studied over two years the incidence of headache as the initial and isolated clinical manifestation of adult patients suffering from intracranial tumors (n = 183). Fifteen patients (8%) exhibited headache as their first and isolated clinical manifestation. Age, sex, neoplasm localization, or pathological diagnosis did not correlate with the presence of headache. Posterior fossa location and hydrocephalus, though not reaching statistical significance, were more frequent in patients who presented with headache as the first symptom. At the moment of diagnosis, 59 (31%) of the patients admitted to headache, though only 1 out of the 15 patients starting as headache still had this symptom as the only manifestation. From our experience in adults, isolated headache for longer than 10 weeks will only exceptionally be secondary to an intracranial neoplasm.