Breast cancer is one of the most cancers in women of developed and developing countries. The optimum management of which requires a multidisciplinary approach including the use of certain biochemical and histopathological markers. The effect of polysaccharide spirulina along zinc oxide nanoparticles on MNU induced mammary carcinogenesis was investigated in female Sprague rats. Injection of N-methyl N-Nitrosourea induced a significant increase in ALT, AST, Mammary MDA and serum NO levels. On other hand marked depletion in mammary GSH, CAT, SOD and GPx. These changes were confirmed by histopathological changes that observed after MNU intoxication. Administration of polysaccharide spirulina and ZnO nanoparticles was able to mitigate mammary carcinogenic damage induced by MNU as evidence to pronounced curative effect against lipid peroxidation, serum NO level and deviated enzymatic variables as well as maintained glutathione status, antioxidant enzymes in addition histopathological changes directed toward control. The results of the present study suggest that polysaccharide spirulina and ZnO nanoparticles have potential to exert curative effects against mammary carcinogenesis.