METHODS A medical centre in Taipei, Taiwan. OBJECTIVE To investigate the trend and characteristics of patients with non-tuberculous mycobacteria (NTM) related skin and soft tissue infection. METHODS A total of 63 patients with culture-proven diseases were identified from January 1997 to December 2004. The medical records of all patients were reviewed. RESULTS Twenty-seven patients were infected with rapidly growing mycobacteria (RGM), 19 with Mycobacterium marinum, six with M. avium complex (MAC), five with M. kansasii and six with other species. Most patients presented with a protracted cutaneous lesion without systemic symptoms, and two thirds of the patients had a history of exposure. Seventy-three per cent of the lesions involved the extremities. Underlying illness with suppressed immunity was documented in 30.2% of the patients, and was most prevalent in patients with MAC (100%) and M. kansasii (60%). Of the patients, 62% underwent at least one surgical intervention, and 77.8% received treatment with different antimicrobial combinations. Most patients (86%) recovered completely. Granulomatous inflammation was found in 88.9% of biopsied tissue associated with M. marinum infection, 31.8% with RGM and 25.0% with MAC. CONCLUSIONS A combination of surgery and antimicrobials cured most patients with microbiologically proven localised NTM skin and soft tissue infection.