Infections by Aeromonas spp. are a rare cause of systemic infection in normal and immunocompromised hosts. We report the cases of two patients with acute non-lymphoblastic leukemia who developed septic shock by Aeromonas species with unusual soft-tissue complications. One patient who was undergoing consolidation chemotherapy developed septic shock by Aeromonas hydrophila with rhabdomyolysis and subsequent soft-tissue destruction consistent with myonecrosis. She recovered with combination antibiotic therapy and supportive care. The second patient developed neutropenia due to ganciclovir treatment for post-allogeneic transplant cytomegalovirus antigenemia. He developed a rapidly progressive septic shock due to Aeromonas sobria with rhabdomyolysis, multi-organ failure and bilateral lower limb myonecrosis, and died within 48 hours. The portal of entry was not identified in either case. These cases confirm the potentially aggressive nature of these bacteria in neutropenic cancer patients with an unusual tendency to produce muscular and soft-tissue destruction.