microRNAs (miRNAs) bind to the 3' untranslated regions (UTRs) of messenger RNAs, where they interfere with translation of genes that regulate cell differentiation, apoptosis and tumourigenesis. The histone methyltransferase SET8 has been reported to methylate TP53 and regulate genomic stability. We analysed a single nucleotide polymorphism (rs16917496) within the miR-502 miRNA seed region at the 3' UTR of SET8 in small-cell lung cancer (SCLC) patients. The SET8 CC+CT genotype was identified to be independently associated with longer survival in SCLC patients by multivariate analysis (relative risk, 0.453; 95% CI 0.217-0.944; p=0.035). The analysis of genetic polymorphisms in miRNA binding sites may help to identify patient subgroups at high risk of poor outcome.