Introduction. This case of herpes virus–induced panniculitis originally diagnosed as pyoderma gangrenosum (PG) illustrates the need for a high index of suspicion for atypical causes of cutaneous ulcers in patients who are immunocompromised. Case Report. A 79-year-old male presented with a 3-month history of a painless chronic ulcer on the left buttock that was refractory to antibiotic therapy and intralesional corticosteroid. The medical history was notable for diabetes mellitus type 2 and rheumatoid arthritis managed with long-term methotrexate and low-dose prednisone. Because the patient initially had a painful and enlarging skin ulcer after intralesional treatment with corticosteroids, an undermined and violaceous ulcer, and an autoimmune condition, PG was suspected at the initial evaluation. A subsequent skin biopsy to complete the workup confirmed the unexpected diagnosis of herpetic panniculitis. The patient was started on antiviral therapy; a prolonged therapeutic and suppressive dose was required. This case highlights the importance of skin biopsy in the diagnosis of chronic ulcers to rule out infectious etiologies. Maintaining a high index of suspicion for rare causes of cutaneous ulcers in the patient with immunosuppression is paramount. Conclusions. Herpes virus infection is only one atypical cause of ulcerative nodules in the immunocompromised patient. Skin biopsy should be considered in the immunocompromised patient with presumed PG that is not responding to standard of care treatment.