Organ failure secondary to fibrosis is the main cause of morbidity and death in patients with systemic sclerosis. Gastrointestinal tract dysmotility is a major visceral manifestation, clinically ranging from an asymptomatic form to severe paresis. Although the oesophagus is the most frequently affected part of the gastrointestinal tract, all other segments can be involved. The present study was undertaken to evaluate the histopathological changes of the gastric wall in a series of full­thickness biopsies from systemic sclerosis patients who underwent gastric surgery due to severe gastroesophageal involvement. Gastric biopsies were processed for light microscopy and transmission electron microscopy. The histological and ultrastructural observations revealed a generalized fibrosis affecting all the gastric wall layers. The most severe changes were observed in the muscularis mucosae and muscle layers. Wide areas of marked focal fibrosis with dense collagen bundles and elastic fibre deposition surrounding smooth muscle cells were found. Myofilaments and thickened dense bodies were severely disarranged or absent in most smooth muscle cells. Nerve fibres showed ultrastructural alterations, such as oedematous axoplasm and scarce cytoskeletal elements. Abundant elastic and collagen fibres enveloped nerve fibres, nerve endings and interstitial cells of Cajal, thereby separating them from smooth muscle cells and blood microvessels. This study provides evidence for a prominent fibrosis and severe ultrastructural alterations of smooth muscle cells and nerve fibres as the main histopathological hallmarks in the gastric wall of systemic sclerosis patients