A 3-yr-old male Rothschild’s giraffe (Giraffa camelopardalis rothschildi) presented for acute swelling caudomedial to the left parietal horn. Following initial diagnostics and supportive treatment, the mass was surgically resected and intralesional chemotherapy was administered. Despite treatment, the giraffe’s condition worsened and euthanasia was performed. Gross necropsy revealed neoplastic invasion and destruction of underlying parietal bone, adjacent horn base, and sinuses, and metastases in the tracheobronchial and mandibular lymph nodes and lung. Histologically, the tumor was composed of packets of anaplastic