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Background Rapidly growing mycobacteria (RGM) are an uncommon cause of infection in breast reconstructive surgery. Patients with breast cancer may be at an increased risk for this infection because of their immunosuppression from chemotherapy, radiation therapy, history of previous surgery, and possible local lymphedema. Methods We retrospectively reviewed all cases of mycobacterial infection occurring in patients with breast cancer from January 2005 to January 2015 at the Moffitt Cancer Center. Results Thirteen isolates were identified with 11 cases occurring unilaterally and 2 cases bilaterally. The median age was 54.8 years (range, 37–77). The median time from onset of symptoms to diagnoses was 6.3 weeks (range, 2–32 weeks). Fifty-five percent of patients had a history of previous chemotherapy and 36% of previous radiotherapy. In 64% (n = 7) of the patients, the infection presented after mastectomy with a tissue expander. The tissue expander (n = 8) or the silicone implant (n = 1) was removed, and 2 patients had no foreign material. The most common isolates were Mycobacterium abscessus (n = 9), followed by Mycobacterium fortuitum (n = 2). Mycobacterium fortuitum isolates were susceptible to ciprofloxacin, trimethoprim/sulfamethoxazole, linezolid, and amikacin. All M. abscessus isolated were susceptible to clarithromycin (100%), some isolates were susceptible to amikacin, but all were resistant to ciprofloxacin, doxycycline, minocycline, moxifloxacin, and trimethoprim/sulfamethoxazole. The treatment regimen was individualized with all patients receiving combination of antibiotics with mostly azithromycin and another agent. There was no mortality in any of the cases. All patients were cured after surgical extraction and antibiotic treatment. Conclusions Rapidly growing mycobacteria infection after breast cancer reconstructive surgery is infrequent, with a low prevalence similar to other published case series in patients without cancer. Rapidly growing mycobacteria should be considered in patients with infections who do not respond to usual antibiotic therapy. Mycobacterium abscessus and M. fortuitum were the most common causes of these RGM infections. The removal of the prosthetic device is a fundamental component for treatment success along with combination antibiotic therapy on the basis of susceptibility testing.