This case series describes hepatocellular neoplasms in 10 Nile lechwe (Kobus megaceros) at two separate zoological institutions in Florida. Histologically, the neoplasms were classified as hepatocellular carcinoma (n = 7), hepatocellular adenoma (n = 2), and hepatobiliary carcinoma (n = 1). Common clinical signs were nonspecific and included thin body condition (n =7), lethargy (n =6), lameness (n =3), and acute recumbency (n =5). Four males and six females were affected, and the mean age at death was 12.7 yr with a range of 4–18 yr. All cases were diagnosed postmortem, and metastasis to various sites, including lung, lymph nodes, and omentum, was found in 40% of cases (n = 4). A single case of hepatocellular carcinoma in a Nile lechwe was described in 2007; however, this is the first reported series of neoplasms in Reduncinae. The pathogenesis behind the development of hepatocellular neoplasms in Nile lechwe has not yet been identified.