The prognostic implications of the immunophenotype of the tumor-infiltrating lymphocytes in primary cutaneous melanoma are well known. In recent years, the study of this immunophenotype has also resulted in immunotherapeutic consequences. The aims of this study were to characterize the subpopulations of tumor-infiltrating lymphocytes in primary cutaneous melanoma, in cases with and without metastasis, as well as the neovascularization associated with the primary neoplasm, and its influence on the development of metastasis. To this end, the immunophenotype of tumorinfiltrating lymphocytes and the neovascularization of 80 patients with primary cutaneous melanoma (40 each with metastatic and non-metastatic melanoma) were analyzed by immunohistochemistry for CD3, CD4, CD8, FOXP3, PD-1, CD31, and D2- 40 antibodies. We found that higher frequencies of tumor-infiltrating lymphocytes with brisk pattern, and CD4+, CD8+, and CD20+ cells in tumor-infiltrating lymphocytes, and a lower frequency of CD31+ vessels were histopathological features associated with better prognosis in primary cutaneous melanoma. Our results support the notion that immunohistochemical study of tumor-infiltrating lymphocytes and neovascularization in primary cutaneous melanoma may be helpful tools for identifying patients at increased risk of metastasis development.