Introduction The aim of this study was to compare the proteomic profile of periodontal pocket tissues with that of corresponding gingival crevicular fluid (GCF), and to search for similarities in their proteomic profile. Material and Methods Four patients suffering from moderate or severe chronic periodontitis, needing surgical periodontal treatment, were selected. Immediately before the periodontal surgery, GCF samples were taken by means of filter paper strips positioned in the gingival sulcus correspondent to periodontal pockets. Then, periodontal pocket tissue, harvested during surgery, was adequately stored for proteomic analyses. Results Using an image analysis software for proteomic data, we found almost the same protein expression profile in GCF and pocket tissue from each patient. Accordingly, in our patients we found no statistically significant correlation between the quantitative proteomic profile of GCF and pocket tissue. Only one band (that of K immunoglobulin) resulted statistically different between GCF and pocket tissue proteome in all patients (p=0.008). Conclusions The protein network of the periodontal pocket does not influence significantly the GCF protein network. The periodontal pocket and the GCF are similar as far as the proteomic networks are concerned, but the GCF does not seem suitable to study on the pathogenesis of periodontal disease.