Rapidly growing mycobacteria have occasionally been reported to cause catheter-related infections. We report a case of a central venous catheter-related bacteremia, caused by Mycobacterium smegmatis, in a patient with cancer. Cultures of the catheter tip and blood cultures grew M smegmatis and Enterococcus faecalis. The patient responded to catheter removal and a 3-month course of antibiotics (doxycycline and ciprofloxacin). Based on our experience and the reported experience with other rapidly growing mycobacteria, M smegmatis catheter-related bacteremia should be treated with catheter removal and a course of appropriate antibiotics, based on in vitro susceptibility testing.