Introduction. Non-O1/non-O139 is a rare strain of Vibrio cholera that has been documented to cause significant morbidity and mortality in the immunosuppressed population. Case Presentation. A patient with multiple myeloma develops non-O1/non-O139 Vibrio cholera septicemia, leading to multiorgan failure and ultimately death. Discussion. An exceedingly rare strain of Vibrio cholera, non-O1/non-O139, may be an important factor of morbidity and mortality in certain immunosuppressed populations, such as patients with multiple myeloma and malignancies. Conclusion. Bacteremia involving generally noninvasive microbes, such as non-O1/non-O139 Vibrio cholerae, can have significant deleterious effects in the immunosuppressed patients as shown by this case report. Physicians need to be more diligent when treating these patients.