Background Sweet Syndrome is an acute, febrile neutrophilic dermatosis that is characterized by painful red lesions, fever, and neutrophilia with histological findings of dermal neutrophilic infiltrate. Neutrophilic Dermatosis of the Dorsal Hands is a localized variant of Sweet Syndrome. Neutrophilic Dermatosis of the Dorsal Hands presents with focused lesions on the dorsal hands, most commonly between the index finger and thumb, typically with fewer systemic manifestations. This condition presents significant diagnostic challenges as it can mimic infectious processes, potentially leading to delayed appropriate treatment. Case Information A 64-year-old male presented to the emergency department with wounds on the bilateral hands. He reported injuring his right hand three weeks prior to presentation that then progressively enlarged over two weeks. The patient noticed the onset of a wound on his left hand despite no injury or trauma. One week before hospital admission, the patient was prescribed trimethoprim-sulfamethoxazole and clindamycin. Despite antimicrobial treatment his wounds continued to worsen. The patient reported that he had occasional fevers but denied other systemic symptoms. In the hospital he was given IV antibiotics and initial work-up complete blood count and complete metabolic panel were performed without clinically significant findings. X-ray of the hands showed soft tissue swelling with polyarticular degenerative joint disease. Blood and wound cultures showed no growth. Due to the atypical presentation dermatology was consulted. Physical exam showed edematous red plaques with overlying hemorrhagic crust extending from the thumb to the dorsal hands bilaterally. Clinically, the presentation was consistent with neutrophilic dermatosis of the dorsal hands, however, to confirm the diagnosis and rule out infection biopsies were performed. The biopsies showed a neutrophilic infiltrate with spongiosis and eosinophils without fungal or atypical mycobacterial growth on cultures which confirmed the diagnosis. The patient was initiated on topical fluocinonide ointment twice daily under occlusion at the time of the biopsy. The patient reported significant improvement in pain within 1 day of receiving treatment. Learning Points Neutrophilic Dermatosis of the Dorsal Hands requires high degree of clinical suspicion. The condition can have multiple etiologies, including drug-induced, paraneoplastic, and idiopathic causes. It is essential in neutrophilic conditions to rule out infection. Early recognition and appropriate diagnosis can prevent unnecessary antibiotic and surgical interventions. This case demonstrates a key diagnostic criterion of Neutrophilic Dermatosis of the Dorsal Hands – rapid improvement within 24 hours of appropriate therapy – while providing valuable insight into the variable progression and healing stages of this condition.