MUC1 is a highly glycosylated glycoprotein that is often overexpressed in adenocarcinomas. MUC1 has molecular diversity because of a variable number of tandem repeats (from 25-125 repeats) in the extracellular domain of its core protein. MUC1 plays an important role in facilitating invasion and metastasis of malignant cells, and it also inhibits anti-cancer immune activity against malignant cells. We hypothesize that MUC1 allele length polymorphism (variable number of tandem repeats) is associated with development of lung adenocarcinoma. We evaluated MUC1 gene polymorphism using Southern blot analysis of peripheral blood from patients with non-small cell lung cancer (n=56), patients with benign respiratory disease (n=52), and healthy volunteers (n=52). We found that large MUC1 allele length was significantly associated with lung adenocarcinoma but not with squamous cell carcinoma of the lung. Adenocarcinoma patients with a homozygous large MUC1 genotype had a worse prognosis than patients with a heterozygous (large + small) MUC1 genotype or a homozygous small MUC1 genotype. These results suggest that the large MUC1 allele is associated with susceptibility to lung adenocarcinoma and poor prognosis.