AIM. To assess the prognostic value of cytotoxic CD8-positive Т-lymphocytes of the reactive tumor microenvironment in diffuse large B-cell lymphoma (DLBCL). MATERIALS & METHODS. The study enrolled 124 patients with newly diagnosed DLBCL. All patients received the standard R-CHOP first-line immunochemotherapy. Immunochemistry and morphometry were used to assess the relative count of CD8-positive Т-lymphocytes in the biopsy samples of lymph nodes or other tumor tissues. In each biopsy sample, 20 fields of view were analyzed to assess the mean relative count of CD8-positive Т-lymphocytes in the reactive tumor microenvironment. Т-cells were counted by double-blind technique. Patients were aged 23–80 years (median 59 years); there were 62 women and 62 men. RESULTS. Obtained by ROC-analysis, the threshold value of the CD8-positive Т-lymphocyte count in the reactive tumor microenvironment was 13 %. The subthreshold relative count of cytotoxic CD8-positive Т-lymphocytes (≤ 13 %) was associated with extranodal lesions in DLBCL patients as well as with the lack of complete response to the R-CHOP first-line therapy and worse progression-free (PFS) and overall survival (OS) rates. In the group with the above-threshold (> 13 %) count of CD8-positive Т-lymphocyte, the 5-year PFS was 60 % (median not reached), in the group with the subthreshold count it was 45.3 % (median 39 months; p = 0.036); the 5-year OS was 78.3 % (median not reached) and 45.3 % (median 40 months) in the groups with the above- and subthreshold CD8+ T-cell counts, respectively (p = 0.001). CONCLUSION. The results of the present study clearly indicate the need to assess the count of cytotoxic CD8-positive Т-lymphocytes of the reactive tumor microenvironment in DLBCL patients as early as on diagnosis verification. It is likely that this approach will allow clinicians to more accurately predict the course of DLBCL.