OBJECTIVE Invasive Mycobacterium marinum disease (tenosynovitis and osteomyelitis) may be an increasingly common manifestation of M. marinum infection that presents unique diagnostic and therapeutic challenges. We conducted a retrospective case series and literature review of M. marinum infection to better understand the clinical spectrum of invasive versus cutaneous disease. METHODS We reviewed electronic medical records for all M. marinum infections at Duke University Medical Center from January 1, 1996 to April 30, 2014. Published case series of M. marinum infection since 1990 reporting >5 cases were systematically ascertained and reviewed. RESULTS Twenty-eight cases of M. marinum infection were identified from our institution. Twenty cases (87 %) involved aquatic exposure, and 26 (93 %) involved finger and/or hand lesions. Median time to diagnosis was 3.5 months. Nineteen (68 %) cases had invasive infection, and 9 (32 %) were cutaneous; invasive infection was more common with older age. Granulomatous inflammation and acid-fast bacilli were noted on pathologic examination in 11 (58 %) and 3 (16 %) cases, respectively. Primarily monotherapy was used in 2 (12 %) cases, dual therapy in 8 (47 %) cases, and three-drug therapy in 7 (41 %) cases; three-drug therapy was more common with invasive infection. Median duration of treatment was 5 months. Adjunctive surgery was performed for 18 (95 %) cases of invasive infection and 4 (44 %) of cutaneous infection. Twenty-one (75 %) cases improved, while 7 (25 %) were lost to follow-up. CONCLUSIONS Distinguishing between invasive and cutaneous M. marinum infection may have important consequences in terms of antibiotic choice and need for adjunctive surgery.