The phenomenon of multidrug resistance (MDR) represents the cross-resistance among a number of unrelated chemotherapeutic drugs and is one of the major causes of chemotherapy failure in many tumors due to its multifactor origin. These factors includes alterations in DNA repair, defects in genes controlling apoptosis, increased intracellular drug detoxification, and activation or overexpression of drug export proteins. Not much is know about the molecular interactions that apparently contribute to the altered signaling pathways and proteins involved in this resistance. Thus, in order to characterize, at molecular level, the protein profile related to multidrug resistance in this work, we took advantage of the proteomic approach and compared the proteomic profile of K562 and Lucena -1 cell lines. K562 cell line is a human erythroleukemia cell line and Lucena, is a K562/VCR resistant cell line with MDR characteristics, which was developed by continuous exposure to increasing concentrations of the alkaloid vincristine. One milligram of each cell was precipitated and used in the 2-D gels. The proteins were separated using a 11cm ImmobilineDrystrip (GE) of pH 4-7, for 78kVh in a Multiphor II (GE), and for the second dimension, a 8-18% gradient SDS-PAGE gel was used. The gels were analyzed and the differential protein-spots were identified by Mass spectrometry in a MALDI-TOF-TOF instrument (Applied Biosystems). We identified 250 proteins in each gel, and 25 protein expressed in Lucena. The protein spots present only in Lucena cell line represents the proteins involved in the MDR phenotype in chronic myeloid leukemia model. From them, value information can be obtained for the improvement of cancer treatment, by overcoming resistance mechanisms.