The study documented the emergence of new forms of resistant bacilli (totally drug-resistant [TDR] or super extensively drug-resistant [XDR] tuberculosis [TB] strains) among patients with multidrug-resistant TB (MDR-TB). Susceptibility testing against first- and second-line drugs was performed on isolated Mycobacterium tuberculosis strains. Subsequently, the strains identified as XDR or TDR M tuberculosis were subjected to spoligotyping and variable numbers of tandem repeats (VNTR). Of 146 MDR-TB strains, 8 XDR isolates (5.4%) and 15 TDR isolates (10.3%) were identified. The remaining strains were either susceptible (67%) or had other resistant patterns (20%). Overall, the median of treatments and drugs previously received by MDR-TB patients was two courses of therapy of 15 months' duration with five drugs (isoniazid [INH], rifampicin [RF], streptomycin, ethambutol, and pyrazinamide). The median of in vitro drug resistance for all studied cases was INH and RF. The XDR or TDR strains were collected from both immigrants (Afghan, 30.4%; Azerbaijani, 8.6%; Iraqi, 4.3%) and Iranian (56.5%) MDR-TB cases. In such cases, the smear and cultures remained positive after 18 months of medium treatment with second-line drugs (ethionamide, para-aminosalicylic acid, cycloserine, ofloxacin, amikacin, and ciprofloxacin). Spoligotyping revealed Haarlem (39.1%), Beijing (21.7%), EAI (21.7%), and CAS (17.3%) superfamilies of M tuberculosis. These superfamilies had different VNTR profiles, which eliminated the recent transmission among MDR-TB cases. The isolation of TDR strains from MDR-TB patients from different regional countries is alarming and underlines the possible dissemination of such strains in Asian countries. Now the next question is how one should control and treat such cases.