The aim of this study was to investigate the clinical, microbiological, and pathological characteristics and the outcomes of skin and soft-tissue infection (SSTI) caused by non-tuberculous mycobacteria (NTM). Medical records of 50 patients with SSTI caused by NTM identified from 2005 to 2008 and 63 patients previously reported in a medical centre from 1997 to 2004 were reviewed. The annual incidence (per 100 000 outpatients and in-patients) ranged from 0·57 in 2005, 0·38 in 2007, to 1·1 in 2008, with an average of 0·62/100 000. From 1997 to 2008, the average incidence was 1·39/100 000 patients. The average annual incidence of SSTI caused by NTM was 0·62/100 000 outpatients and in-patients during 2005 and 2008. Of the total of 113 patients identified during the 12-year period, patients infected with Mycobacterium fortuitum and M. marinum were younger than those infected with M. avium-intracellulare complex (MAC) (36 and 44 years vs. 55 years, P=0·004 and P=0·056, respectively), and were more likely to have previous invasive procedures than those infected with MAC and M. abscessus (81·8% and 72·0% vs. 27·8% and 54·8%, P=0·007), and less likely to have associated immunosuppression (9·1% and 24% vs. 66·7% and 45·2%, P=0·006). Granuloma was more often observed in immunocompetent patients (60·1% vs. 40%, P=0·019), and in M. marinum-infected specimens (78·3%). There were significant differences in the demographic and clinical features of patients with NTM SSTI, including immunosuppression, trauma experience, and depth of tissue infections.