BACKGROUND Different medication classes have been implicated in cutaneous eruptions that may lead to significant morbidity and mortality. In drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, the patient may initially present with a cutaneous eruption and hematologic abnormalities which can lead to acute visceral organ involvement if the offending drug is not discontinued. There is also a potential for long-term sequelae such as autoimmune disorders. CASE REPORT A 47-year-old woman with an unknown past medical history and no known drug allergies was admitted to the Behavioral Health Unit, where she was diagnosed with disorganized schizophrenia and started on olanzapine. On day 17 of admission, she developed a diffuse, macular, and erythematous rash on her abdomen, which spread to involve over 50% of her total body surface area. Occipital and posterior auricular lymphadenopathy was present. The patient was treated with prednisone and diphenhydramine. Olanzapine was subsequently discontinued and the patient's rash cleared up. CONCLUSIONS This case report highlights the challenges in diagnosing DRESS syndrome and the potential for antipsychotics to cause DRESS syndrome. DRESS syndrome is a clinical diagnosis augmented by laboratory tests with a wide range of patient presentations. Although there are probability criteria to assist with diagnosis, not all patients will fall exactly into these criteria, which can lead to missed diagnoses and poor patient outcomes. A challenge with DRESS syndrome diagnosis is the latency period between drug initiation and cutaneous eruption. Thus, in differential diagnoses for skin eruptions, temporal associations (minutes, days, weeks) with medications are crucial.