Leptotrichia spp. are anaerobic, pencil-shaped, Gram-negative rods that are part of the normal oral and intestinal human flora. Although not typically considered pathogenic, invasive Leptotrichia infections have been reported in immunosuppressed patients. A perceived rise in the identification of Leptotrichia spp. at our institution prompted a retrospective evaluation of these infections. Laboratory and clinical records were reviewed to identify Leptotrichia culture-positive patients. Over a 5-year period, 68 Leptotrichia-positive specimens were identified. Of these, 21% (14/68) were identified in original samples submitted from 13 different patients at our institution, and the remainder (79% [54/68]) were unknown isolates referred from outside hospitals for molecular identification. All in-house Leptotrichia were identified from blood cultures. Only 64% (9/14) of these grew on solid media, and 5 were a part of polymicrobial bacteremias containing other enteric pathogens. All local patients were receiving chemotherapy and a majority received hematopoietic stem cell transplant (HSCT) (11/13). All had neutropenic fever with symptoms of mucositis and/or enteritis. Most of the HSCT patients (73% [8/11]) were autologous recipients hospitalized after recent high-dose chemotherapy for multiple myeloma. L. hongkongensis, a novel species, was found in the majority of myeloma cases (63% [5/8]). In conclusion, we suggest that Leptotrichia spp. may be an underappreciated cause of bacteremia, particularly in multiple myeloma patients receiving cytotoxic chemotherapy for autologous HSCT. In our cohort, these infections were associated with neutropenic fever from an enteric source, and most isolates remained sensitive to standard antibiotics.