Abstract Medication reactions, infectious etiologies, graft vs. host disease, serum sickness, and serum sickness-like reaction are the most common conditions that cause skin fever and rashes in immunosuppressed patients. In addition to this long list of diseases, severity of the primary disease and deterioration in the patient’s health status can make the diagnosis difficult. Furthermore, cutaneous and histological similarities in these mentioned conditions can be confounding. Here, we present a 16-year-old male patient with acute myeloid leukemia suffering from skin rashes and fever that appeared following a chemotherapy course leading to bone marrow suppression. We aim to discuss the differential diagnosis and share the diagnostic challenges that we already have experienced after immunoglobulin M-enriched polyclonal immunoglobulin.