Helicobacter pylori is an extra macro- and microdiverse bacterial species, but where and when diversity arises is not well-understood. To test whether a new environment accelerates H. pylori genetic changes for quick adaptation, we have examined the genetic and phenotypic changes in H. pylori obtained from different locations of the stomach from patients with early gastric cancer (ECG) or chronic gastritis (CG). Macroarray analysis did not detect differences in genetic content among all of the isolates obtained from different locations within the same stomach of patients with EGC or CG. The extent and types of functional diversity of H. pylori isolates were characterized by 2-D difference gel electrophoresis (2D DIGE). Our analysis revealed 32 differentially expressed proteins in H. pylori related to EGC and 14 differentially expressed proteins in H. pylori related to CG. Most of the differentially expressed proteins belong to the antioxidant protein group (SodB, KatA, AphC/TsaA, TrxA, Pfr), tricarbon acid cycle proteins (Idh, FrdA, FrdB, FldA, AcnB) and heat shock proteins (GroEL and ClpB). We conclude that H. pylori protein expression variability is mostly associated with microorganism adaptation to morphologically different parts of the stomach, which has histological features and morphological changes due to pathological processes; gene loss or acquisition is not involved in the adaptation process.