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Background: Metastatic brain lesions lead to the most unfavorable prognosis for the course of an oncological disease. Most often, brain metastases arise from primary tumors such as lung cancer, breast cancer, and melanoma. Of particular interest are groups of secondary intracranial tumors without an identified primary focus. Methods of non-invasive differential diagnosis based on a possible histological affiliation, including diffusion-kurtosis magnetic resonance imaging, can improve the diagnostic search for the primary tumor. Aim: The aim of this study is to improve the quality of differential diagnosis for brain metastases of tumors of different primary localization by introducing the diffusion-kurtosis magnetic resonance imaging technique into the magnetic resonance scanning protocol. Methods: Our work included studies of 60 patients who underwent examination and treatment at the N.N. Blokhin National Research Medical Center of Oncology of the Ministry of Health of Russia from October 2019 to March 2022. According to magnetic resonance imaging, metastatic formations were detected in the brain of the patients, with different localizations of the primary tumor. 20 patients were diagnosed with lung cancer (33.3%), 20 patients with breast cancer (33.3%) and 20 patients with melanomas (33.3%). We evaluated the tumor size, diffusion and kurtosis parameters, such as the mean kurtosis, axial kurtosis, radial kurtosis, kurtosis anisotropy, radial diffusion, and fractional anisotropy, and relative anisotropy, axial diffusion of the extra-axonal fluid, radial diffusion of the extra-axonal fluid, axonal fluid fraction, and tortuosity of the diffusion trajectory. Results: Statistically significantly (p 0.05) differing parameters of diffusion and kurtosis in the comparative evaluation of the above indicators were identified in the structure associated with melanoma and lung cancer axial diffusion, fractional anisotropy, relative anisotropy, radial kurtosis and tortuosity of the diffusion trajectory, as well as in the structure of melanoma and breast cancer — axial diffusion, axonal fluid fraction, fractional anisotropy, axial diffusion of extra-axonal fluid, mean kurtosis, relative anisotropy, radial kurtosis and tortuosity of the diffusion trajectory. Conclusion: Diffusion-kurtosis magnetic resonance imaging is a promising technique that allows obtaining additional differential information in the case of metastatic lesions of the brain matter, especially those from an undetected primary focus.