A 2-yr-old, captive, intact female Virginia opossum (Didelphis virginiana) with a 7-mo history of ulcerative dermatitis and weight loss was euthanatized for progressive worsening of clinical signs. Initially the opossum was treated with several courses of antibiotics, both topically and systemically; systemic nonsteroidal anti-inflammatory medication; and, later, systemic glucocorticoids, with no improvement in clinical signs. Histopathologic samples of skin lesions taken 3 mo into the course of disease revealed no evidence of neoplasia; however, cytologic samples of a skin lesion taken 5 mo into the course of disease revealed mature lymphocytes, and were suggestive of cutaneous lymphoma. Postmortem histopathology revealed neoplastic cells consistent with lymphoma; these were found in the haired skin of the forearm, axilla, hind limb, face, and lateral body wall, as well as the liver, kidney, axillary lymph node, heart, and spleen. Multifocal neutrophilic and eosinophilic ulcerative and necrotizing dermatitis and folliculitis of the haired skin were also present. To the authors' knowledge, this is the first documented case of cutaneous lymphoma in a Virginia opossum and the first documented case with visceral metastases in a marsupial.