One hundred and fourteen BALB/cA and 89 hairless (hr/hr, Oslo strain) mice of both sexes were treated topically once a week on the dorsal skin for about 17 months with 18 nmol 12‐0‐tetradecanoyl‐phorbol‐13‐acetate (TPA) in 0.2 ml acetone or with 0.2 ml acetone alone, and observed for up to 24 months. At autopsy all visible lesions and selected areas from the skin, nasal cavities and a number of internal organs were examined microscopically. Only TPA‐treated animals developed epidermal tumours, i. e. squamous cell papillomas and carcinomas, which were the only tumours with a higher incidence in TPA‐treated animals than in controls. The BALB/cA mice developed more epidermal tumours than the hr/hr mice. Other tumours were: reticuloses, malignant lymphomas, lung adenomas, subcutaneous fibrosarcomas, parenchymal adenomas, hemangiomas and one angiosarcoma of the liver, intestinal adenocarcinomas and one granulosa cell tumour of the ovary. Various degrees of amyloidosis in several organs, and subcapsular fusiform cell hyperplasia in the adrenal glands, occurred in both mouse strains. Kupffer cell proliferation was more prevalent in the hr/hr mice treated with TPA than in the controls. This lesion was absent in the BALB/cA strain. Hence, TPA is a weak skin carcinogen for both BALB/cA and hr/hr mice, and multiple skin applications of the dose of TPA used do not alter the frequency of spontaneous internal tumours in these mouse strains.