Corynebacterium striatum is a rare, but likely underreported, cause of serious infections in immunocompromised hosts and generally is susceptible to multiple classes of antimicrobial agents. Here we report the first case of C. striatum infection in a solid organ transplant recipient. Three years after heart transplantation, a 58-year-old man developed bilateral pneumonia and pulmonary embolism. He did not improve with levofloxacin, piperacillin/tazobactam, and heparin treatment. A homogeneous population of abundant gram-positive rods was repeatedly demonstrated in sputum and bronchoalveolar lavage fluid, and C. striatum was grown in pure culture. The isolate was unusual for its multidrug-resistant (MDR) antimicrobial susceptibility pattern. The pneumonia resolved with 4 weeks of vancomycin therapy, in combination with rifampin given only during the first 2 weeks of treatment. The isolation of coryneforms ("diphtheroids") is often attributed to contamination. Their abundant presence on direct examination of specimens and/or their growth in pure culture suggest a pathogenic role, however, and indicate the need for accurate microbiological identification, particularly in immunocompromised hosts who have been hospitalized and previously treated with antibiotics. Combination therapy that includes vancomycin may be the most prudent treatment for MDR C. striatum infections.