Corynebacterium jeikeium is a multidrug-resistant gram-positive bacterium of the human skin flora and one of the most clinically important nondiphtherial corynebacteria in the acute care setting. C. jeikeium can cause different forms of infections, especially in immunocompromised patients with underlying risk factors and comorbidities. C. jeikeium was initially described in 1976 as a highly resistant coryneform bacteria causing severe sepsis in patients with hematologic malignancies and profound neutropenia. C. jeikeium infection has also been reported in the setting of endocarditis, septicemia, meningitis, pneumonia, and soft tissue infections. Management of disseminated C. jeikeium infection in immunocompromised cancer patients can be challenging due to its high virulence and rapid skin colonization. We present two cases of disseminated C. jeikeium infection in patients with acute myelogenous leukemia (AML) and underlying comorbidities. Both patients presented with neutropenic fever resistant to initial standard empiric antibiotic therapy.