Human herpesvirus type 1 (HHV-1) is widely dispersed among the human population. Although infection is often asymptomatic in humans, nonhuman primates develop a severe and often fatal infection. In August 2006, 13 black-tufted marmosets (Callithrix penincillata) from a group of 14 presented with clinical apathy, anorexia, and ataxia. Physical examination revealed conjunctivitis, erosive or ulcerative lesions on the skin, and swollen lymph nodes. Of the 14 animals captured, 10 died. Grossly, ulcers and erosions were observed on the skin of face, nasal planum, lips, and oral mucosa. Histologically, superficial vesicular and erosive stomatitis with associated basophilic intranuclear inclusion bodies in the squamous epithelium were observed. Swabs from oral lesions and tissue samples from necropsied animals were positive for HHV-1 by nested polymerase chain reaction for eight animals.