Summary A 23‐year‐old Trakehner mare was referred to the Department of Large Animal Medicine with an ulcerative cleft tumour dorsal of the anus and in poor body condition. An infiltrative growing squamous cell carcinoma (SCC) was diagnosed. Surgical treatment was not an option because of the tumour localisation and topical chemotherapy caused severe side effects (coprostasis), therefore an immunological therapeutic approach involving autologous monocyte‐derived dendritic cells (DC) presenting tumour antigen on their surface was chosen. Dendritic cells were administered to the patient three times at intervals of four weeks to induce an immune response against the SCC. The tumour regressed in size, the ulcerated surface healed, body condition improved and coprostasis subsided. Six and a half months later small papillomatous neoplasms at the tumour scar led to a fourth treatment. During follow‐up, those recurrences remained indifferent; the mare showed physiological behaviour and returned to leisure riding. This case report describes the effectiveness of so far infrequently described immunotherapy with DC in horses.