Mycobacterium kansasii infections of the skin have been described in 31 previously published cases. The median age of these patients is 43 years, and male patients are more frequently affected than female patients. Most patients (72%) with this infection have some alteration of their immune status, but disseminated infection is relatively uncommon (22%). We present the first reported case of cutaneous M. kansasii infection in a patient with previously diagnosed systemic lupus erythematosus. The clinical presentation is similar to that expected in lupus profundus. While the duration of treatment is long (18 months), this case demonstrates that rifampin combined with at least 2 other antibiotics can provide excellent results. Clarithromycin has demonstrated encouraging in vitro results against M. kansasii but has not yet been reported for treatment of cutaneous infections.