Although loss of heterozygosity (LOH) on chromosome 18q is frequently found in gastric cancer, the clinical significance of this abnormality has not been well documented. We examined LOH on chromosome 18q22-23 in DNA extracted from the tissues of gastric cancer patients using the PCR-based dinucleotide repeat assay with two microsatellite markers, D18S61 and D18S58. We investigated LOH in 100 samples of DNA extracted from formalin-fixed, paraffin-embedded tissues of cohesive-type gastric cancer patients operated on between 1984 and 1993. Thirty-two of 83 informative cases (39%) showed LOH on chromosome 18q22-23 at one or two loci. The LOH correlated significantly with serosal invasion of the tumor (P = 0.004) and hematogenous recurrence (P = 0.035). In 60 cases who were cured, the 5-year survival rate in patients with LOH (54%) was lower than that in patients without LOH (81%; P = 0.019). These results suggest that 18q22-23 LOH in cohesive gastric cancer is associated with tumor progression and a patient's poor prognosis.