Non-tuberculous mycobacteria are increasingly being recognized as important human pathogens. We present the case of a 44-year-old non-diabetic male who underwent left total knee arthroplasty for degenerative arthritis after trauma. He developed left knee swelling and progressively worsening pain over the next 4 weeks. He was referred for treatment using whirlpool baths and developed a blister at the surgical incision site. Repeated aspirations of the left knee failed to show any growth of organism on routine cultures. He finally underwent explantation of the left knee prosthesis with antimicrobial spacer placement 4 months later. Cultures of three different intra-operative specimens turned positive for Mycobacterium goodii. This infection was successfully treated with combination oral antimicrobials for 6 months. The patient underwent revision left knee arthroplasty subsequently and was symptom-free until his last follow-up visit 1 year later. This patient highlights the importance of testing for mycobacteria in prosthesis-related infections with previously negative routine bacterial cultures.