Recently, there has been an increase in the number of patients with primary multiple malignant tumors, which not only affect one or more organs, but also differ in their histological structure. At the same time, melanoma of the skin is a rare localization among primary malignant neoplasms. This nosology accounts for only 3–5 % of all skin tumors. Melanoma is associated with high mortality due to the development of a pronounced metastatic potential, and therefore the study of this malignant formation is of the greatest relevance. Over the past 50 years, the incidence of multiple primary melanoma has increased significantly. At the same time, the number of patients with more than 2 lesions has increased to 18 % of the number of primary multiple melanomas over the past 50 years. This emphasizes the importance of monitoring patients with melanoma and regularly examining patients for new lesions. This article demonstrates a clinical case of a patient with a confirmed diagnosis of a primary multiple disease with melanoma of the skin and rectum. For skin melanoma, the patient underwent a wide excision of the tumor with inguinal-femoral lymph node dissection on the right. Subsequently, radiation therapy and chemotherapy were performed. Further, during a comprehensive examination, the patient was diagnosed with a malignant neoplasm of the lower ampullar rectum with a transition to the anal canal. The patient underwent laparoscopic-assisted abdominoperineal extirpation of the rectum. Histological analysis revealed nodular melanoma. From the anamnesis of the patient, among the comorbidities, breast cancer, uterine myoma, hemangioma of the liver and lung hamartoma were also identified. The clinical course of all malignant tumors was favorable, without the development of relapses and metastases. The greatest interest in this situation is the primary multiple melanoma in connection with successful treatment with the most unfavorable prognosis. The described clinical observation indicates the need for an in-depth study of cases of primary multiple malignant tumors and the search for mechanisms for a favorable course of malignant neoplasms in this case.