BACKGROUND Tuberculosis (TB), a global public health problem, is a disease with a high incidence and prevalence worldwide. The risk of developing TB increases after starting anti-tumor necrosis factor (TNF) therapy in the management of ulcerative colitis (UC). Isolated neurotuberculosis (NTB) without other manifestations is a rare form of infection in these patients. This article reports a case of a severe UC patient with isolated NTB following long-term therapy with adalimumab and discusses the clinical aspects, diagnosis, management, and prognosis. CASE REPORT A 34-year-old female patient with severe UC with pancolitis reported continuous and progressive holocranial headaches associated with a daily fever of 38°C and night sweats after 4 years of using adalimumab and after being in deep remission. Annually, she was screened for latent TB with chest X-rays and a Mantoux tuberculin skin test, and she always had negative results for TB. On cerebral magnetic resonance imaging with post-contrast sequences, small cortical lesions in the left frontal lobe and 2 larger lesions were visualized and were suggestive of tuberculomas. The initial management consisted of the suspension of immunosuppressive therapy and treatment with rifampicin, isoniazid, ethambutol, pyrazinamide, and prednisone. The patient showed clinical and neurological improvement and was clinically asymptomatic, with no changes in laboratory tests. Also, she had no neurological sequelae and was taking maintenance therapy with prednisone as indicated by the neurologist. CONCLUSIONS Early recognition of symptoms of neurological involvement of TB, suspension of anti-TNF and adequate treatment are fundamental steps to prevent complications.