We reported a case in which multi-drug resistant tuberculosis was recognized after two courses of anti-tuberculosis treatment. A 41-year-old woman who had received two courses of anti-tuberculosis treatment for pulmonary tuberculosis was admitted to our hospital due to productive cough, high fever and positive sputum smear showing acid fast bacillus. In the past treatment, drug susceptibility was unknown because of culture-negative TB. Chest radiograph showed atelectasis of the right upper lobe. The pathological examination of surgically resected lung specimen revealed that atelectasis was formed by a granulation tissue with caseous necrosis progressed to the bronchus wall. We examined cultures three times using both solid and liquid media. Liquid culture of the first time specimen was positive for Mycobacterium tuberculosis after six weeks and multi-drug resistant tuberculosis was recognized on drug susceptibility test. Thereafter she was treated with KM, LVFX, PZA and PAS, and maintained sputum smear negative for 7 months after treatment. Physicians must consider possibility of MDR-TB despite findings showing smear-positive and culture-negative TB.