A case of a malignant schwannoma in a 20-year-old male American buffalo (Bison bison bison) from the Grand Park Zoo, Gyeonggi Province, Republic of Korea is reported. The animal showed no apparent clinical signs before death except for wound on the neck. Grossly, neoplastic nodules of various sizes were observed on the skin, lung, heart, liver, stomach, mesentery and kidney. Histologically, the neoplastic nodules were composed of fusiform cells that formed multidirectional bundles. The tumour cells were arranged in interlacing bands and bundles. The nuclei were atypical, hyperchromatic, with blunt or round ends. In addition, few mitotic figures were observed in the skin, lung, heart, liver, stomach, intestine and kidney. Several immunohistochemical stains, e.g. vimentin, cytokeratin (CK), smooth muscle actin (SMA), S-100 and HMB45, were used in an attempt to differentially diagnose the tumour. The neoplastic cells tested positive to S-100, but negative to vimentin, CK, SMA and HMB45. Based on the above findings, this case was diagnosed as a malignant schwannoma. To the best of our knowledge, this is the first report of a schwannoma in an American buffalo (B. b. bison).