Non-tuberculous mycobacteria are rarely responsible for skin and soft tissue infections. These infections are caused by different mycobacterial species originating from the environment (water, soil, plants, and animals). Various factors influence the clinical manifestation of the cutaneous infection: the immunological situation of the patient, the degree of cutaneous impairment, and the extent of the contact with the contaminated environment. The clinical manifestation is non-specific and often the cause of extensive diagnostic activities. The diagnosis is based on the cultural detection of the causative pathogen. The management of these skin and subcutaneous infections is a challenge for each physician. The treatment comprises administration of several antibiotics and antituberculosis drugs for many months. Surgical procedures are necessary in some patients.