Fever of unknown origin (FUO) is a common syndrome. A total of 94 patients (57 men and 37 women; mean age, 56.3 +/- 19 years, range, 18-86 years) who met the criteria of FUO were included in this study. Mycobacteriosis was diagnosed in 22 (23%) of these patients (13 men and 9 women), including 9 with disseminated disease and 13 with pulmonary disease. There was no significant statistical difference in age, sex, short-term survival status (3 months), and other clinical parameters between patients with and without mycobacteriosis. Clinical manifestations may be specific or nonspecific. The most common initial presentations in patients with mycobacteriosis were respiratory tract symptoms, mainly of cough and dyspnea, observed in 11 (50%) patients, and disturbance of consciousness in 6 (27%). The associated conditions included malnutrition (4 patients, 18%), diabetes mellitus (3, 14%), and renal failure (3, 14%). Four (18%) patients had a history of pulmonary tuberculosis or tuberculous spondylitis in their early adulthood. The 2 most common findings on chest radiograph were interstitial (41%) and nonspecific infiltrative (32%) patterns. In conclusion, mycobacteriosis remains the leading cause of FUO in southern Taiwan and it is important to screen for this treatable disease in all cases of FUO.