The volume of endoscopic biopsies being performed continues to grow rapidly and they now represent one of the most common specimens encountered in routine surgical pathology practice. It is essential to maintain the balance between the speed and accuracy while integrating emerging sophisticated pathology techniques into endoscopic biopsies in routine practice. Microscopic appearance is virtually diagnostic of certain diseases. In others a diagnosis may be rendered only after correlating the microscopic pattern with clinical clues aided by ancillary tests.