In lymph node melanoma metastases, the expansive proliferation of tumor cells may be compared, structurally and cytologically, to the vertical growth phase (VGP) observed in primary melanoma. Both in VGP and in nodal metastases, tumor infiltrating lymphocytes (TILs) may be present with different patterns. In the evaluation of the primary tumor, these patterns have been defined as brisk, non-brisk, and absent. The histologic slides of regional lymph node metastases, the site of first recurrence in 99 consecutive melanoma patients, were reviewed. Disease-free survival of these cases and whether or not they were treated with rIFN alpha-2A was recorded to identify any relationship among different patterns of TILs, therapy, and prognosis. Of 99 cases, 16 were classified as brisk, 37 as non-brisk, and 46 as absent. At 30 months of follow-up the disease-free survival was 81.3% for brisk cases, 46.8% for non-brisk cases, and 29.3% for absent groups (p = .007). Multivariate analysis confirmed the prognostic value of TILs in predicting disease-free survival in patients with regional node metastases. The difference according to the presence or absence of relapse is particularly evident when comparison is made between treated and untreated patients. In conclusion the evaluation of first-recurrence regional node melanoma metastases for TILs, using the same histopathologic criteria as in VGP of primary melanoma, subdivides the cases in brisk, non-brisk, and absent groups. Also, the presence of these patterns in metastatic node melanoma deposits is correlatable to disease-free survival. Our results further stress the difference of prognosis patients treated with rIFN alpha-2A compared to the untreated group. The TILs evaluation may prove useful in selecting those melanoma stage II patients who will best respond to therapy with biologic response modifiers, because the TILs may be the local immune effector cell targets of rIFN alpha-2A or of other biologic agents.