The object of this study was to evaluate activities of thymidylate synthetase (TS) and thymidine kinase (TK) in relation to histopathological features of human mammary carcinomas, as well as clinical classification of patients. The TS and TK are key enzymes on the de novo and salvage pathways, respectively, for pyrimidine nucleotide synthesis. High TS and TK activities have been found in rapidly proliferating tissues. Clinical stage and TNM post-surgical histopathological classification of 20 patients with mammary carcinomas, during the period of 1988-1991, and TS and TK activities in each carcinoma were determined. Elevated TS and TK activities in mammary carcinomas corresponded to progressively worse clinical stages. Papillotubular carcinomas showed lower enzyme activity than that of solid-tubular and scirrhous types. TS activities continued to rise as the malignant invasion became more severe. The clinical prognosis of patients with mammary carcinomas appears to depend on the de novo synthesis of DNA in carcinomas.