The isoflavonoid genistein, the aglycone of the heteroside genistin, possesses preventive effect on coronary heart disease and osteoporosis, antioxidant, anthelmintic, antineoplastic and anti-inflammatory properties. Much research has been undertaken regarding the action of genistein on cancer-preventing/treating effects, especially on breast and prostate cancer. The aim of this study was to analyze the effect of this compound in vivo by observing tumor size, metastasis potential and melanization in a mouse model of murine melanoma, employing the B164A5 melanoma cell line and C57BL/6J mice. Genistein decreased the tumor volume and weight by approximately 30%. Non-invasive measurements for both melanin and erythema showed that genistein reduced the quantity of melanin and the degree of erythema in direct proportion to the number of days of treatment. HE analysis diagnosed malignant melanoma in both groups, but no metastasis was recorded in the treated group compared with the liver metastasis in the untreated group after a period of 15 days of experiment at a dose of 15 mg/kg body weight of genistein. Genistein showed beneficial effects regarding tumor size, metastasis potential and melanization in a B16 mouse model of murine melanoma.