In childhood malignancies such as retinoblastoma and Wilms tumour, of which both familial and sporadic forms exist, recessive mutations of presumed differentiation genes have been implicated in tumorigenesis. A proportion of cases appear with microscopically visible chromosome deletions which indicate the regions where the genes concerned are located. Mutation or loss of one allele causes a cancer predisposition. For tumour development functional loss of the remaining normal allele is also required. In cancers with both familial and sporadic forms, molecular-genetic studies have shown that deletion is often one of the mutational events. Although familial and sporadic forms have never been distinguished in lung cancer, deletions of the short arm of chromosome 3 have been described for small cell lung cancer (SCLC), but their general occurrence in SCLC has been disputed. Using a molecular-genetic approach, we here present evidence for a consistent deletion at the chromosomal region 3p21, not only in SCLC, but in all major types of lung cancer.