Proteomic analysis of core needle biopsy (CNB) sample from patient populations is critical to our understanding of human disease,but has been hindered by its particular small size.Here,we present a method for the proteomic analysis of CNB sample based on the two dimensional electrophoresis.Proteins were extracted directly from 3 rat liver CNB specimens and a human prostate CNB sample.respectively.24 cm Immobiline DryStrip (pH 3-10NL) and 12.5% SDS-PAGE were introduced to separate the proteins.Interesting spots were analyzed by MALDI TOF/TOF mass spectrometry after tryptic digestion.With this method,consistent electrophoretic patterns of more than 2 500 protein spots were reproducibly obtained after silver staining,from rat liver CNB specimens.Qualitatively and quantitatively reproducible results also yield when the method was applied to a human prostate CNB sample.57 stochastically selected protein spots were analyzed by MALDI TOF/TOF moss spectrometry.and were identified with high confidence including faint ones.This simple and reproducible approach raises the opportunity of defining key molecular events of human disease pathologies.