Mycobacterial infections of the skin classically cause a granulomatous tissue reaction. We have observed a suppurative pattern of inflammation associated with infections by rapid-growing Mycobacterium species in immunocompromised patients. We report 6 cases in skin and soft tissue with an unusual but consistent lack of a predominance of granulomatous inflammation. Of the 6 cases, 4 had predominantly (approximately 75%) suppurative inflammation, 1 case predominantly demonstrated (approximately 75%) a mix of acute and chronic inflammation, and 1 case showed an approximately equal contribution of suppurative and granulomatous inflammation. All 6 cases showed abscess formation and numerous acid-fast bacilli (AFB) on AFB stain and were confirmed by tissue culture. Of these 6 cases, 2 had microabscesses with central pseudocysts harboring microorganisms. Five patients were taking oral prednisone, and 1 had an uncharacterized immunodeficiency. These cases highlight the need for awareness of this unusual manifestation of infection with rapid-growing Mycobacterium species, particularly in immunocompromised patients.