There are currently no accepted clinical guidelines for the surveillance of first-degree relatives (FDRs) of gastric cancer patients. The existence of intestinal metaplasia, as well as altered mucin expression, might be associated with an increased risk for gastric cancer. In the present study we aimed to investigate the mucin phenotype of individuals with a family history of gastric cancer.We included FDRs of gastric cancer patients. Individuals with functional chest pain served as controls. Upper endoscopy including extensive biopsy according to the Olga protocol was performed. Immunohistochemical staining for MUC1, MUC2, MUC5AC, and MUC6 was performed. Sera were assayed for pepsinogen I and II. Helicobacter status was determined through Giemsa staining and serological tests.Forty FDRs and eight controls were included; the mean age was 46.7 ± 12.0 years. In both the study group and the control group there were no gross endoscopic findings and no histological evidence of intestinal metaplasia. Superficial MUC1 expression was significantly increased in the study group (47.5 vs. 0%; P=0.01). There was no difference in the expression of deep MUC1, MUC2, MUC5AC, or MUC6 between the groups, nor was there a difference in pepsinogen I/II levels or Helicobacter pylori exposure (35.0 vs. 25.0%; P=0.46).Despite normal appearing mucosa and the absence of intestinal metaplasia according to histological analysis, FDRs of gastric cancer patients show increased expression of MUC1, which may serve as a predictor of future intestinal metaplasia, dysplasia, and cancer. Further studies are needed to verify these findings and their implications.