Diagnosing of melanoma is based on conventional excisional biopsy. Suspected melanoma necessitates the radical removal of the whole element in order to avoid early metastases, which seems to be unjustified to a patient in the case of ultimate diagnosis of a benign process. Apprehension for the consequences of “undue” biopsy forces doctors to postpone its implementation, which leads to late diagnosis and increased mortality. Optical coherence tomography (OCT) can be used as an alternative to biopsy. Objective — the objective of the study was to explore the use of OCT and polarization-sensitive OCT modification (PS OCT) for the in vivo diagnosis and differential diagnosis of melanoma. Material and methods. The study included 24 patients with melanoma. We carried out the clinical, dermatoscopic, OCT, and PS OCT studies (a total of 1580 images were analyzed) followed by surgical excision of tumors, histological examination of post-operative material, and histo-tomographic comparison. Diagnostic accuracy, sensitivity, and specificity of the method was assessed using a “blind” melanoma and melanocytic nevi image recognition test. Results. It was found that OCT and PS OCT images of melanoma are characterized by specific features, which enable the diagnosis and differential diagnosis of melanoma from melanocytic nevus at the pre-histologic stage to develop adequate tactics, as evidenced by high indices of sensitivity (84.2—94.5%), specificity (84.7—93.9%), and diagnostic accuracy (87.8—88.3%) of the method.