A patient is described who had severe hyperplastic gastropathy as the presenting manifestation of systemic lupus erythematosus (SLE). Aggressive immunosuppressive therapy with systemic corticosteroids and immunoglobulins resulted in complete remission of lupus, and a prompt clinical and radiological regression of hyperplastic gastropathy. Hyperplastic gastropathy is an uncommon gastric illness, which is usually idiopathic but rarely is associated with Helicobacter pylori infection, cytomegalovirus infection or lymphocytic gastritis. Three previous case reports have noted a response of idiopathic hyperplastic gastropathy to systemic corticosteroid treatment, yet none of the presented patients had a systemic inflammatory disease. The presented case is the first in the medical literature in which hyperplastic gastropathy is directly linked to the development of clinical and laboratory manifestations of SLE. We suggest that hyperplastic gastropathy be added to the list of rare gastrointestinal manifestations of SLE, and that autoimmune disease be considered a possible cause of hyperplastic gastropathy. As such, any patient with symptomatic idiopathic hyperplastic gastropathy accompanied by other evidence of systemic inflammation should be considered for SLE evaluation and immunosuppressive treatment.