Based on the assumption that proteins can emanate from tumour to serum, we investigated whether serum low molecular weight proteins (LMW) can discriminate lung cancer patients from healthy donors. Pooled sera from 20 lung cancer patients matched in sex (men), histological type (adenocarcinoma) and stage (IIIB and IV) and from 20 healthy donors (men) were submitted to 2-DE coupled to MALDI-TOF peptide mass fingerprinting. Results of 2D-E/ MALDI-TOF showed five up regulated proteins (immunoglobulin lambda chain, transthyretin monomer, haptoglobin-alfa 2 and two isoforms of serum amyloid protein) and one down regulated (fragment of apolipoprotein A-I) in patients. All differentially expressed proteins, except immunoglobulin, may be acting as a non-specific sign of inflammation in cancer and transthyretin monomer may act as a possible blood marker to CSF barrier disruption that occurs, e.g., in cerebral metastasis. In conclusion, this work shows the usefulness of 2D-gel electrophoresis and mass spectrometry proteomic techniques for the identification of up- and down-regulated proteins in serum from adenocarcinoma lung cancer patients.