Citrus canker disease caused by the bacterial pathogen Xanthomonas axonopodis pv. citri (Xac) is considered a threat to the Brazilian citriculture because of its easy dissemination and the absence of commercial resistant plants. Hypertrophy and hyperplasia are the first microscopic symptoms of the disease. In this work we compared the gene expression profile of orange Citrus sinensis leaves inoculated with a suspension of Xac and Xanthomonas axonopodis pv. aurantifolii (Xaa), which is not pathogenic to orange but causes canker in lemon. The isolation and characterization of differentially expressed genes induced by these bacteria was done using both suppression subtractive hybridization (SSH) and differential display PCR (DD PCR). Finally, Real Time Quantitative PCR (RT qPCR) validated and compared the levels of induction or repression of genes modulated by the pathogens. Differentially expressed genes were grouped into functional categories (i.e. cell wall remodeling, vesicle trafficking and transport, auxin response elements, gibberellins synthesis and disease response among others). Furthermore, we found that cell wall remodeling genes and auxin response elements that account for cell enlargement (hypertrophy) are strongly induced by Xac and moderately by Xaa. This kind of host manipulation could explain the facility Xac has in order to break the leaf epidermis and disseminate. Moreover, our work is the first approach in order to understand the complex biochemical pathways triggered early during the plant pathogen interaction and leading to the canker disease.