A proteomic approach was applied to study the protein expression profile of peripheral T-cells derived from patients at the onset of different B-lymphoproliferative diseases, because a rising interest in specific actions played by T-cells in such pathologies has emerged. Decreased levels of profilin-1 and cofilin-1 and increased levels of coronin1A and prohibitin were found in patients, compared with healthy controls. The protein-protein interaction network of these proteins was studied using a web-based bioinformatics tool, highlighting the actin cytoskeleton regulation as the main biological process involved in peripheral T-cells of such patients. Unsupervised cluster analysis of protein expression data shows that the recorded alteration of T-cell proteome was specifically induced by B-cell pathologies.