Aim: The retrospective analysis of different types of surgical treatment efficiency among the patients with melanoma showed that preventive lymphatic dissection does not improve 5-year survival rate of patients. At that, the appearance of metastases in regional lymph nodes after the removal of primary tumor, despite a delayed lymphatic dissection, decrease 5-year-old survival rate by half, and the emergence of intradermal metastases decreases it 3 times. To improve the efficiency of melanoma patient treatment, the additional impact on latent tumor cells in the lymphatic skin system and subcutaneous tissue are proposed - the conduct of photodynamic therapy (PDT). Materials and Method: The study included 47 melanoma patients, who had the PDT of zonal areas in skin lymphatic system as a component of combination treatment, which are located between the primary tumor lesion and a regional lymph barrier. Results and Discussion: To perform PDT, the patients had the introduction of photosensitive drug intravenously (Russia) in the dose of 0.3 mg/kg of patient body weight 24 h before the first session of irradiation. Irradiation parameters: Irradiation wavelength - 670 nm, the density of laser energy emission - 50 J/cm2, the power density of laser radiation - 50 mW/cm2, and the number of irradiation sessions - 10-22. The patient follow-up period made 2 years. During this time 4 patients (8.5%) of 47 demonstrated local recurrences, including 2 patients - in the skin of the limb, distal to the resected tumor, where the exposure was not performed. This indicates that a photodynamic action should be carried out on the area of the skin distal to the level of the primary tumor. Conclusions: The performed studies showed that PDT in combination with surgery methods is a promising one for the treatment of the patients with melanoma. The obtained results are the basis for further research in this direction. © 2018 Drug Invention Today.