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The Beijing/W genotype is one of the major molecular families of <i>Mycobacterium tuberculosis</i> complex (MTBC), responsible for approximately 50% of tuberculosis (TB) cases in Far East Asia and at least 25% of TB cases globally. Studies have revealed that the Beijing genotype family is associated with a more severe clinical course of TB, increased ability to spread compared to other genotypes, and an unpredictable response to treatment. Based on the profile of spacers 35–43 in the Direct Repeat (DR) locus of the MTBC genome determined by spoligotyping, classical (typical) and modern (Beijing-like) clones can be identified within the Beijing family. While the modern and ancient Beijing strains appear to be closely related at the genetic level, there are marked differences in their drug resistance, as well as their ability to spread and cause disease. This paper presents two cases of drug-resistant tuberculosis caused by rare mycobacteria from the Beijing family: the Beijing 265 and Beijing 541 subtypes. The genotypes of isolated strains were linked with the clinical course of TB, and an attempt was made to initially assess whether the Beijing subtype can determine treatment outcomes in patients.