Background: Mycobacterium chelonae is a ubiquitous, rapidly growing, nontuberculous mycobacteria that primarily affects immunocompromised patients. The most common presentation is an atypical, chronic skin and soft tissue infection. Due to its high resistance rate, early diagnosis based on clinical suspicion, risk factor assessment, and exposure history is crucial for initiating appropriate multi-drug treatment. Methods: We report two cases of M. chelonae skin and soft tissue infections, one presenting with localized disease and the other with disseminated involvement. One case had a specific exposure to fish-related activities, a risk factor more commonly associated with Mycobacterium marinum infections rather than M. chelonae. Results: One of the cases involved osteomyelitis and tenosynovitis which are rare presentations of M. chelonae infection. While the limbs are the most commonly affected sites in disseminated M. chelonae infections, involvement of the lower extremities, as seen in one of our cases, is rarely reported. Treatment posed challenges due to antibiotic resistance and patient tolerance. However, in both cases where follow up was possible, prolonged multi-drug therapy led to complete resolution of the lesions. Conclusions: These cases highlight the importance of considering M. chelonae in chronic skin and soft tissue infections, especially in patient with relevant exposures or immunosupression. Uncommon presentations require a high index of suspicion. Given the challenges of treatment resistance and patient tolerance, prolonged multi-drug therapy remains essential for successful outcomes.