BACKGROUND: (18)F-FDG-PET/CT has been widely used in the staging of malignant lymphomas, and accepted as a tool for response assessment. Among PET parameters, the most frequently studied is maximal standardized uptake value (SUVmax). Metabolic tumor burden (MTB) is a parameter in which both metabolic tumor volume (MTV) and tumor activity are integrated. Here, we analyzed the prognostic value of SUVmax, SUVsum (sum of the SUVmax), whole-body MTV (MTVwb) and MTBwb from baseline and interim PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). MATERIAL AND METHODS: Twenty-nine patients with histologically proven DLBCL were imaged by PET/CT before treatment (Exam I), and one week after the first dose of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy (Exam II). Biopsy specimens were examined by an expert hematopathologist, the Ki-67 proliferation index (PI) was estimated for each biopsy site from the MIB-1 stained sections. The response evaluation was performed after chemotherapy completion (6-8 cycles). RESULTS: All patients had one or more visualized lymphomatous lesions on (18)F-FDG-PET/CT. The SUVmax of the whole-body (BmSUVmax) was higher than the SUVmax at biopsy site (BxSUVmax) (mean: 20.1 vs. 17.3, p < 0.01). The PI correlated with the BxSUVmax (p < 0.05). One week after chemotherapy, SUVmax, SUVsum, MTVwb, and MTBwb decreased significantly (p < 0.01, respectively), SUVsum, MTVwb and MTBwb at Exam II correlated with chemotherapy response at treatment completion (p < 0.05, respectively). CONCLUSION: SUVmax is more accurate to detect tumor aggressiveness than biopsy in DLBCL, since BmSUVmax represents the most aggressive tumor of the patient. Interim PET/CT as early as one week after R-CHOP therapy predicts response. Thus, it could be used as a tool for guidance of risk stratification in DLBCL.