Primary drug resistance is defined as the presence of resistant strains of Mycobacterium tuberculosis in a patient with no history of prior anti-tuberculosis chemotherapy. In Japan, a recent study shows that the prevalence of primary resistance has been stable for two decades and that primary multidrug-resistant tuberculosis (MDR-TB) is rare, which suggests the effectiveness of tuberculosis control. We presented four cases of primary MDR-TB that we had experienced from 1984 to 1997, and discussed an issue about diagnosis and treatment of primary MDR-TB. Of the four patients, two young men received surgical resection, which has resulted in a favorable outcome. Of the other two patients, one responded to long-term chemotherapy with ethambutol, ofloxacin and enviomycin. There have been no recurrence so far in the three cases. The rest case died due to progression of tuberculosis. Two of the four patients had been in contact with relatives who had died of MDR-TB. In conclusion, all the tuberculosis patients should be suspected to be primary MDR-TB when they had a history of a contact with a tuberculosis patient in whom chemotherapy had not been successful, and once patients are diagnosed as MDR-TB, surgical intervention should be considered as an adjunctive treatment. To prevent the emergence of primary MDR-TB, it is important to treat MDR-TB patients appropriately and to implement the infection control program.