Background: TPS (Tissue Polypeptide Specific Antigen) is defined by a monoclonal antibody against an epitope of the soluble Tissue Polypeptide Antigen (TPA). It is considered to be a tumor marker indicating cellular proliferation, not just tumor load. Serial values of this unique marker during tumor therapy might, therefore, be more sensitive and earlier signs of tumor response than conventional tumor markers. Patients and Methods: Serial values of TPS and TPA were determined in 50 consecutive tumor patients and compared with simultaneously measured conventional tumor markers. Evolution of TPS and TPA values over time was compared with the clinical response to tumor therapy. Results: Distribution and levels of both TPS and TPA were similar, and a significant correlation was found between them (R = 0.877, p = 0.0001). In 30 patients the value of TPS was higher than that of TPA, and in 20 cases TPS values were lower than TPA values. No significant correlation to conventional tumor markers was found. Values of both TPS and TPA were lower in patients with lymphomas than in patients with gastrointestinal cancers, breast or lung cancers. Although we have some evidence that in some cases a response may be detected somewhat earlier by TPS than by clinical criteria or by conventional tumor markers, the ability of TPS to reliably predict a clinical response was generally poor. Even frankly discordant evolutions of TPS, TPA and clinical response were seen. Conclusions: Based on our results, the serial analysis of TPS and TPA for use in the decision making process during follow-up of unselected cancer patients cannot be recommended. The actual clinical value of determining TPS remains to be demonstrated.