A 5-yr-old tiger salamander (Ambystoma tigrinum) presented with a 0.5-cm-diameter, 0.2-cm raised swelling of the head with no previous history of trauma to that area. Repeated aspirations and imaging were nondiagnostic, and a surgical biopsy confirmed a melanophoroma. The mass was surgically resected and liquid nitrogen cryotherapy was used to treat the wound area for residual neoplastic cells. The ambient environmental temperature was also lowered from 23°C (73.4°F) to 13°C (55.4°F) to prevent neoplastic cell regrowth. The salamander died 9 months later, and a review of the tissues revealed no evidence of the melanophoroma at the surgical site and an incidental odontoma of the jaws. This case highlights the successful use of surgery, cryotherapy, and environmental temperature modification to treat a melanophoroma in a tiger salamander.