Mycobacterial infections are a well-known, potentially serious, albeit infrequent complication of solid-organ transplantation. Nontuberculous mycobacteria generally account for less than 50% of all such isolates in this patient population. Mycobacterium xenopi, an environmentally ubiquitous organism and common contaminant of hospital hot water systems, is a particularly uncommon isolate after transplantation and has never been reported in heart allograft recipients. We report the occurrence of cavitary M. xenopi infection in an immunocompromised heart transplant recipient in which all the diagnostic criteria of the American Thoracic Society were met. To our knowledge, this is the first such case in a heart transplant recipient described in the literature. Despite therapy, to which the isolates were sensitive in vitro, the patient developed extensive lung cavitation and nodules and succumbed 5 months later to allograft rejection, chronic allograft vasculopathy, and pneumonia.