ATP-thymidine 5'-phosphotransferase (TK) is a cellular enzyme involved in DNA synthesis, activated during the G1/S phase of the cell cycle. Elevated TK serum levels can be found in cancer patients due to the active proliferation of tumor cells. TK serum activity was tested by a radioenzymatic technique (Prolifigen TK REA, Sangtec Medical, Sweden) based on the conversion of 125 I deoxyuridine to 125 I deoxyuridine monophosphate. A total of 181 patients were enrolled in this study: 133 lymphomas (Hodgkin, HL and Non-Hodgkin, NHL) 48 benign diseases including acute (n = 17) and chronic inflammatory diseases (n = 13), myocardial infarction (n = 11), liver cirrhosis (n = 2), renal failures (n = 2), and diabetes (n = 3). Lymphoma patients were classified according to the Ann Arbor staging system, and 103 NHL patients were classified according to the Working Formulation histologic grade (21 low, 72 intermediate, and 10 high grade lymphomas). The patients were treated with standard chemo-radiotherapeutic protocols according to the stage and the histologic grade; the evaluation of the response to the treatments and the follow-up were performed according to the serial examinations currently used in our Institute. Given a TK cut-off of 5 U/L, the diagnostic sensitivity of TK test at lymphoma presentation was 81.8% and 75.7% in HL and NHL patients, respectively. Values exceeding 50 U/L were found only in NHL patients. The overall sensitivity of TK resulted higher than that of LDH (16.7%), copper (42.6%), IgG (23.5%), IgM (26.8%) and IgA (9.8%).(ABSTRACT TRUNCATED AT 250 WORDS)